Circulating Tumor Cells Are Associated with Recurrent Disease in Patients with Early-Stage Non–Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy

Abstract

Purpose: Although stereotactic body radiotherapy (SBRT) is effective in early-stage non-small cell lung cancer (NSCLC), approximately 10%-15% of patients will fail regionally and 20%-25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT.Experimental Design: Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled. CTCs were enumerated by utilizing a GFP-expressing adenoviral probe that detects elevated telomerase activity in cancer cells. Samples were obtained before, during, and serially up to 24 months after treatment. SBRT was delivered to a median dose of 50 Gy (range, 40-60 Gy), mostly commonly in four to five fractions (92%).Results: Thirty-eight of 92 subjects (41%) had a positive CTC test prior to SBRT. A cutoff of ≥5 CTCs/mL before treatment defined favorable (n ¼ 78) and unfavorable (n ¼ 14) prognostic groups. Increased risk of nodal (P ¼ 0.04) and distant (P ¼ 0.03) failure was observed in the unfavorable group. Within 3 months following SBRT, CTCs continued to be detected in 10 of 35 (29%) subjects. Persistent detection of CTCs was associated with increased risk of distant failure (P ¼ 0.04) and trended toward increased regional (P ¼ 0.08) and local failure (P ¼ 0.16).Conclusions: Higher pretreatment CTCs and persistence of CTCs posttreatment is significantly associated with increased risk of recurrence outside the targeted treatment site. This suggests that CTC analysis may potentially identify patients at higher risk for regional or distant recurrences and who may benefit from either systemic therapy and/or timely locoregional salvage treatment.

Circulating Tumor Cells and Metabolic Parameters in NSCLC Patients Treated with Checkpoint Inhibitors

“…Similar to Krebs et al, in our study, the presence and the number of CTC were influenced by previous lines of therapy. Indeed, patients with a positive history for previous therapy had a mean number of CTC lower than those who underwent ICI as first-line therapy (p = 0.004) [7]. As a consequence, the presence of CTC in the peripheral blood after chemotherapy might suggest the grade of response to treatment or, in other words, the aggressiveness of the tumor determining how fast cancer can return after a macroscopic response.…”

“…Some studies have demonstrated that CTC enumeration is related to poor prognosis in different metastatic malignancies, including lung, breast, colorectal, prostate, and gastric cancer. Furthermore, molecular characterization of CTC might expand our knowledge on tumor heterogeneity, especially in patients for whom tissue biopsies are difficult to perform [4][5][6][7][8].…”

Longitudinal Change of Circulating Tumor Cells During Chemoradiation Therapy and Its Correlation with Prognosis in Advanced Non-Small Cell Lung Cancer Patients

“…For lung cancer, one study shows that the pre-chemoradiation CTCs is negatively associated with PR in advanced NSCLC patients [22]. Furthermore, a study displays that elevated pre-radiation CTCs and persistence of CTCs post-radiation are associated with higher recurrence risk outside the targeted treatment site in early stage NSCLC patients [26]. Another study displays that higher pre-chemoradiation CTCs level is an independent predictive factor for worse OS in small cell lung cancer patients [20].…”

Hepatocellular Carcinoma–Circulating Tumor Cells Expressing PD‐L1 Are Prognostic and Potentially Associated With Response to Checkpoint Inhibitors

“…(19) CTCs are easily accessible through a simple blood draw, amenable to serial sampling, and recognized as a potential alternative to invasive, technically challenging tissue biopsies. (20) Although the prognostic significance of CTCs is established in several malignancies, (21,22) data for their utility in HCC remain limited. (23) More recently, subset characterizations of CTCs expressing various phenotypic profiles such as epithelial-to-mesenchymal transition markers (24,25) and stem cell markers (26) have been shown to have significant prognostic utility.…”