Circulating DNA in Non-small Cell Lung Cancer Patients: Relation to Tumor Burden, Disease Prognosis and Risk for Cancer Recurrence, With Emphasis on Tumor Heterogeneity and Treatment Response
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Disease-free survival
研究概览
简要总结
- The investigators will prospectively recruit 100 NSCLC patients. The cfDNA samples will be gathered before the surgery and postoperatively 4-6 weeks after surgery and at 6 and 12 months follow-up visits.
- This study aims to investigate the role of ctDNA in NSCLC patients treated with curative intent surgery.
- Preoperative ctDNA will be compared to primary tumor DNA to investigate the concordance of mutations and gained mutations from possible primary tumor cancer stem cell.
- Preoperative ctDNA findings will be tested for associations with baseline characteristics as well as clinically important factors such as TNM stage, histopathological findings, and tumor volume.
- The investigators aim to identify molecular residual disease (MRD) using multiple ctDNA samples after the surgery and search the associations with clinical recurrence and survival, with possible correlation to palliative chemotherapy response
- Using multiple ctDNA samples, the investigators will gather information about tumor heterogeneity, diversity of disease genotypes, and dynamic changes in ctDNA.
- If additional data from palliative immunotherapy (PD-L1 inhibitors) is available, the effect of this will be evaluated in the study.
详细描述
Plasma liquid biopsy is rapidly emerging non-invasive diagnostic tool that could be used as a surrogate for tumor biopsy or disease activity. Circulating cell-free DNA (cfDNA) is short fragment double stranded DNA that is present in blood. Ultrasensitive mutation specific techniques based on polymerase-chain-reaction (PCR) analysis are required to detect mutations and alterations in circulating tumor cells. Early studies based on a small number of patients indicate that ctDNA analyses could be used for molecular testing, cancer detection, surrogate for tumor burden or activity, and treatment monitoring in solid tumors.
In the current study the role of ctDNA from plasma in surgically treated early stage NSCLC patients will be investigated. The investigators aim to collect a prospective cohort of a hundred patients with preoperative and follow-up samples as well as diagnostic tissue specimen. The investigators hypothesize that longitudinal ctDNA-samples could be used as prognostic marker for recurrence and survival. Finding postsurgical positive ctDNA could aid us to identify patients who would benefit from adjuvant chemotherapy before clinical recurrence.
Study design and ethical considerations
This is a prospective, non-interventional, single arm study that will be conducted in collaboration with Helsinki Biobank. It is estimated that cohort of 100 patients will provide with ample sample size, as 30-40% will develop a recurrence during the 5 year follow up. A preliminary agreement with Helsinki Biobank about the sample collection and storage has been made. There will be no additional study appointments as all the control visits and study samples are scheduled according to normal clinical protocol. The patients will be recruited from 1.5.2019 to 31.12.2020. The recruited patients will provide both a written informed consent for this study and a Helsinki Biobank consent that covers plasma and surgical samples. Participants can withdraw the consent at any time of the study. The Biobank samples will be taken simultaneously with clinical samples, minimizing the additional harm to participants. A Helsinki University Hospital (HUS) institution review board permission (HUS 60/2019) and ethical statement has been granted (455/2019). The study will be conducted in accordance with the Declaration of Helsinki.
Patients
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The inclusion criteria into this study is histologically confirmed NSCLC eligible for surgical treatment and naïve for systemic oncological treatments with either formalin-fixed paraffin-embedded tissue or fresh frozen tissue sample available.
排除标准
- •prior metastatic solid cancer, hematological malignancy, known hereditary cancer syndrome, and pregnancy
结局指标
主要结局
Disease-free survival
时间窗: 2 years
Lead time to tumor recurrence detection by blood circulating tumor DNA versus clinical recurrence
次要结局
- ctDNA locoregional versus distant recurrence(4 years)
- The correlation of ctDNA and clinical features(2 year)
- The concordance of ctDNA and tumor DNA(1year)
- Prognostic impact of ctDNA(4 years)
研究者
Ilkka Ilonen
Principal Investigator
Helsinki University Central Hospital