Circulating Tumor Cells: When a Solid Tumor Meets a Fluid Microenvironment

2011 Background: Leptomeningeal metastasis (LM) involves seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges. Proton craniospinal irradiation (pCSI) has been shown to be potentially effective for patients with solid tumor LM. We evaluated whether CSF circulating tumor cells (CSF-CTC) and neuroimaging correlate with outcomes in patients with LM treated with pCSI. Methods: We reviewed a single-institution retrospective database of patients treated with pCSI for LM between 2018-2020 who had ≥ 3 months (mos.) follow-up and identified 58 patients. Pre-pCSI CSF-CTC using CellSearch and magnetic resonance imaging (MRI) data, and post-pCSI CSF-CTC nadir before initiation of new cancer-directed therapy were assessed. The optimal cutoff for pre-pCSI CSF-CTC was determined using maximally selected rank statistics. Kaplan Meier analysis was used to identify univariate correlates with CNS progression free survival (CNS PFS) and overall survival (OS), calculated from start of pCSI. Multivariate Cox proportional hazards modeling was used to test independence of univariate associations. Results: The median follow-up for patients who were censored (n = 15, 26%) was 15 mos. (interquartile range (IQR): 9 -21). Most patients were diagnosed with lung (n = 27, 47%) or breast cancer (n = 22, 38%). The median CNS PFS and OS were 6 mos. (IQR: 3 – 9) and 8 mos. (IQR: 5 – 18), respectively. Of the 49 patients with pre-pCSI CSF-CTCs analyzed, CSF-CTCs were identified in 43 (88%). Pre-pCSI CSF-CTC< 53/3mL was associated with improved CNS PFS (11.8 vs 6.0 mos., p = 0.01), and a trend toward improved OS (16.7 vs 7.7 mos., p = 0.08). On pre-pCSI MRI, patients with parenchymal brain metastases (n = 33, 57%) had worse OS (6.7 vs 12.7 mos., p = 0.01) but not CNS PFS. Patients with both brain and spine LM (n = 42, 72%) compared to those only one site or no visible disease (n = 16, 28%) showed worse CNS PFS (5.8 vs 7.5 mos., p = 0.03) and OS (7.7 vs 16.7 mos., p = 0.05). In a multivariate model, pre-pCSI CSF-CTC was significantly associated with CNS PFS (p = 0.03) while brain and spine LM on MRI was not (p = 0.20) No patient had an increase in CSF-CTC immediately post-pCSI, and in those with both detectable pre-pCSI CSF-CTCsand a post-pCSImeasurement(n = 29, 50%), the median decrease at nadir was 37/3mL (range: 0-200) occurring at a median of 1.6 mos. (range: 0.5 -5.2). A decrease in CSF-CTC > 37/3mL was associated with improved CNS PFS (7.1 vs 4.4 mos., p = 0.04) but not OS (12.5 vs.7.7 mos., p = 0.2). Conclusions: Proton CSI is an effective treatment for patients with solid tumor LM and can result in prolonged disease control in some patients. Lower CSF-CTC count prior to pCSI and larger changes after pCSI are predictive of survival outcomes, arguing for early pCSI intervention for solid tumor LMD. Early treatment escalation after pCSI can be considered for patients with high pre-pCSI CSF-CTC and a smaller nadir post-pCSI.

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Prospective characterization of circulating tumor cells using a nanotechnology-based capture system in oligometastatic patients undergoing definitive radiation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.11533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 11533-11533 ◽

Cited By ~ 3

Author(s):

Daniel Paul Lindsay ◽

Joseph Michael Caster ◽

Kyle Wang ◽

Ja Hye Myung ◽

Ronald C. Chen ◽

...

Keyword(s):

Tumor Cells ◽

Clinical Outcomes ◽

Circulating Tumor Cells ◽

Solid Tumor ◽

Predictive Biomarker ◽

Disease Recurrence ◽

Concurrent Chemotherapy ◽

Post Treatment ◽

Prognostic Information ◽

Curative Therapy

11533 Background: Circulating tumor cells (CTCs) can provide prognostic information in select patients with advanced cancers. We have developed a sensitive and specific CTC capture system (Oncosensor) which may predict clinical outcomes in patients undergoing definitive radiation for head and neck cancers. There is increasing interest in utilizing potentially curative metastasis-directed therapy for patients with oligometastatic solid-tumor malignancies. There is currently no biomarker to predict the success of this approach in most patients. The purpose of this prospective study is to investigate the potential utility of CTCs as a predictive biomarker for patients with oligometastatic cancer undergoing potentially curative therapy. Methods: Eligible patients had a metastatic solid-tumor malignancy with 3 or fewer metastases. All sites of disease were treated with definitive radiation or surgery. Concurrent chemotherapy was allowed. Peripheral blood (7 ml) was collected prior to starting, first week, mid-point, end RT, and every 4 to 12 weeks post RT. CTCs were quantified using the Oncosensor platform. We then assessed correlations between CTCs (baseline, end treatment, and changes during treatment) and clinical outcomes using multivariate analysis. Results: Baseline CTCs were detected in 20/20 enrolled patients with a mean baseline of 32/ml which decreased to a mean of 14/ml at the end of treatment. There was no association between pretreatment CTCs and clinical outcomes (p = 0.81). There was a significant association between post-RT CTCs and PFS (p = 0.039, HR 1.07 per CTC). Our data also suggest that post-treatment CTC monitoring may be able to detect early disease recurrence. Among the 4 patients with documented clinical failures and post-treatment CTC monitoring, all 4 had increases in CTCs with or prior to clinical or radiographic disease progression, with 1.6 to 7.3 fold increase at the time of progression compared to the prior time point. Conclusions: Our pilot data suggest CTCs may provide a predictive biomarker for patients with oligometastatic disease and could potentially provide a novel marker of disease recurrence.

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