Frequency of Circulating Tumor Cells (CTC) in Patients with Brain Metastases: Implications as a Risk Assessment Marker in Oligo-Metastatic Disease.

Klaus Pantel,Simon Joosse,Manfred Westphal,Sonja Loges,Sabine Riethdorf,Christian Bernreuther,Carlotta Riebensahm,Annkathrin Hanssen,Malte Mohme,Janna-Lisa Velthaus,Markus Glatzel,Katrin Lamszus,Harriet Wikman,Lars Berger

doi:10.3390/cancers10120527

Klaus Pantel, Simon Joosse + Show 12 more

Open Access

https://doi.org/10.3390/cancers10120527

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Abstract

Forty percent of non-small cell lung cancer (NSCLC) patients develop brain metastases, resulting in a dismal prognosis. However, patients in an oligo-metastatic brain disease setting seem to have better outcomes. Here, we investigate the possibility of using circulating tumor cells (CTCs) as biomarkers to differentiate oligo-metastatic patients for better risk assessment. Using the CellSearch® system, few CTCs were detected among NSCLC patients with brain metastases (n = 52, 12.5% ≥ two and 8.9% ≥ five CTC/7.5 mL blood) and especially oligo-metastatic brain patients (n = 34, 5.9%, and 2.9%). Still, thresholds of both ≥ two and ≥ five CTCs were independent prognostic indicators for shorter overall survival time among all of the NSCLC patients (n = 90, two CTC ≥ HR: 1.629, p = 0.024, 95% CI: 1.137–6.465 and five CTC ≥ HR: 2.846, p = 0.0304, CI: 1.104–7.339), as well as among patients with brain metastases (two CTC ≥ HR: 4.694, p = 0.004, CI: 1.650–13.354, and five CTC ≥ HR: 4.963, p = 0.003, CI: 1.752–14.061). Also, oligo-brain NSCLC metastatic patients with CTCs had a very poor prognosis (p = 0.019). Similarly, in other tumor entities, only 9.6% of patients with brain metastases (n = 52) had detectable CTCs. Our data indicate that although patients with brain metastases more seldom harbor CTCs, they are still predictive for overall survival, and CTCs might be a useful biomarker to identify oligo-metastatic NSCLC patients who might benefit from a more intense therapy.

Highlights

The formation of metastasis is the limiting factor of survival for most carcinoma patients
Metastases hereby originate from single tumor cells, i.e., circulating tumor cells (CTCs), which were initially able to detach from the primary tumor, survive in the circulation, and colonize distant target tissues [3,4]
CTC detection in the peripheral blood of non-small cell lung cancer (NSCLC) patients and patients suffering from other tumor entities can be used for prognosis estimation, and to predict time to metastatic relapse and overall survival [5,6,7,8]

Summary

Introduction

The formation of metastasis is the limiting factor of survival for most carcinoma patients. Despite some improvements in treatment options, mortality among non-small cell lung cancer (NSCLC) still remains extremely high. Forty percent of non-small cell lung cancer (NSCLC) patients already present. Cancers 2018, 10, 527 with metastases at initial diagnosis (stage IV), resulting in a median overall survival of only four months in men and five months in women [1,2]. Metastases hereby originate from single tumor cells, i.e., circulating tumor cells (CTCs), which were initially able to detach from the primary tumor, survive in the circulation, and colonize distant target tissues [3,4]. CTC detection in the peripheral blood of NSCLC patients and patients suffering from other tumor entities can be used for prognosis estimation, and to predict time to metastatic relapse and overall survival [5,6,7,8]. CTCs are currently discussed as a promising liquid biopsy marker

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