The Christie NHS Foundation Trust, Withington, Greater Manchester, M20 4BX, UK; The University of Manchester, Oxford Road, Manchester, Greater Manchester, M13 9PL, UK.
Cancer Research UK Manchester Institute Cancer Biomarker Centre, University of Manchester, Alderley Park, Macclesfield, SK10 4TG, UK.
Lung Cancer. 2020 Dec;150:216-220. doi: 10.1016/j.lungcan.2020.11.002. Epub 2020 Nov 5.
Small cell lung cancer (SCLC) has a dismal prognosis. Circulating tumour cells (CTCs) can be used to generate CTC derived explants (CDX) for the study of SCLC biology and the development of novel therapeutics. We investigated whether there are demographic or clinical predictors of the success of CDX generation, and whether CDX models are representative of the SCLC patient population.
This was a single centre, retrospective analysis of SCLC patients who had participated in the CHEMORES Study. Paired blood samples were donated for CTC enumeration and CDX generation attempt at pre-treatment baseline, disease progression and intervening timepoints. Clinical and demographic data was collected from electronic records, and analysed for differences between patients whose samples did and did not generate a CDX.
231 paired blood samples were taken from 147 patients. 45 CDX were generated from 34 patients. CTC number was significantly higher in blood samples which successfully generated a CDX than those which didn't, at both baseline (p=<0.0001) and progression (p = 0.0001). The group with successful blood samples had a poorer performance status (p = 0.0067), and a higher proportion of patients with chemorefractory disease (p = 0.0077). Both progression free survival (PFS) (p = 0.0132) and overall survival (p=< 0.0001) were significantly shorter for patients with successful samples.
Patients whose samples generate CDX models may have a higher disease burden and more aggressive disease. Thus, insights gained by study of SCLC CDX may have a significant impact, particularly in the SCLC subpopulation with the greatest clinical need.
小细胞肺癌（SCLC）预后不良。循环肿瘤细胞（CTC）可用于生成 CTC 衍生外植体（CDX），以研究 SCLC 生物学和开发新的治疗方法。我们研究了 CDX 生成成功是否存在人口统计学或临床预测因素，以及 CDX 模型是否代表 SCLC 患者人群。
这是一项 CHEMORES 研究中 SCLC 患者的单中心回顾性分析。在治疗前基线、疾病进展和中间时间点，患者同时捐献配对血样进行 CTC 计数和 CDX 生成尝试。从电子病历中收集临床和人口统计学数据，并分析样本生成 CDX 的患者与未生成 CDX 的患者之间的差异。
从 147 名患者中采集了 231 对血液样本。从 34 名患者中生成了 45 个 CDX。在基线（p<0.0001）和进展（p=0.0001）时，成功生成 CDX 的血液样本中的 CTC 数量明显高于未成功生成 CDX 的血液样本。成功样本组的表现状态较差（p=0.0067），且更多患者患有化疗耐药性疾病（p=0.0077）。有成功样本的患者无进展生存期（PFS）（p=0.0132）和总生存期（p<0.0001）明显更短。
成功生成 CDX 模型的患者可能疾病负担更高，疾病更具侵袭性。因此，对 SCLC CDX 的研究可能会产生重大影响，特别是在最需要临床治疗的 SCLC 亚群中。
