Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Clin Cancer Res. 2020 May 15;26(10):2372-2380. doi: 10.1158/1078-0432.CCR-19-2158. Epub 2020 Jan 22.
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.
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%).
Thirty-eight of 92 subjects (41%) had a positive CTC test prior to SBRT. A cutoff of ≥5 CTCs/mL before treatment defined favorable ( = 78) and unfavorable ( = 14) prognostic groups. Increased risk of nodal ( = 0.04) and distant ( = 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 ( = 0.04) and trended toward increased regional ( = 0.08) and local failure ( = 0.16).
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.
尽管立体定向体部放疗（SBRT）在治疗早期非小细胞肺癌（NSCLC）方面非常有效，但仍有约 10%-15%的患者会出现区域性复发，20%-25%的患者会出现远处转移。我们评估了一种新型的循环肿瘤细胞（CTC）检测作为 SBRT 后复发风险增加的预后标志物。
前瞻性纳入 92 例 T1a（64%）、T1b（23%）或 T2a（13%）期 I NSCLC 患者，均接受 SBRT 治疗。利用表达 GFP 的腺病毒探针检测癌细胞中端粒酶活性升高来计数 CTC。在治疗前、治疗期间和治疗后 24 个月内连续采集样本。SBRT 中位剂量为 50Gy（范围 40-60Gy），最常见的分割方式为 4-5 次（92%）。
92 例患者中有 38 例（41%）在 SBRT 前 CTC 检测呈阳性。治疗前 CTC 检测值≥5 CTCs/mL 定义为有利（78 例）和不利（14 例）预后组。不利组中，淋巴结（ = 0.04）和远处（ = 0.03）失败的风险增加。在 SBRT 后 3 个月内，35 例患者中有 10 例（29%）继续检测到 CTCs。持续检测到 CTCs 与远处失败（ = 0.04）的风险增加相关，与区域（ = 0.08）和局部（ = 0.16）失败的风险增加趋势相关。
较高的治疗前 CTCs 和治疗后 CTCs 的持续存在与靶区外复发风险的增加显著相关。这表明 CTC 分析可能有助于识别局部或远处复发风险较高的患者，并可能受益于全身治疗和/或及时的局部区域挽救治疗。
