Abstract
BackgroundThe Response Evaluation Criteria in Solid Tumors (RECIST) guideline and Common Terminology Criteria for Adverse Events (CTCAE) criteria are used to assess chemotherapy efficiency and toxicity in patients with advanced lung cancer. However, no real-time, synchronous indicators that can evaluate chemotherapy outcomes are available. We wanted to evaluate tumor response and toxicity in advanced lung cancer chemotherapy by using a novel synchronous strategy.ResultsWe enrolled 316 patients with advanced lung cancer who were treated with cisplatin-based therapy and followed up them for 3 years. Plasma was obtained before and after every chemotherapy cycle. We quantitative assayed total plasma DNA and methylation of the APC/RASSF1A genes. Four parameters were assessed: methylation level before chemotherapy (meth0 h), methylation level 24 h after chemotherapy (meth24 h), total plasma DNA concentration before chemotherapy (DNA0 h), and total plasma DNA concentration 24 h after chemotherapy (DNA24 h). When meth24 h > meth0 h of at least one gene was used to predict tumor response, the correct prediction rate was 82.4 %. Additionally, patients for whom DNA24 h/DNA0 h ≤ 2 had mild toxicities. Therefore, meth24 h > meth0 h and DNA24 h/DNA0 h ≤ 2 were defined as criteria for better tumor response and fewer adverse events with a high correct prediction rate (84.7 %).ConclusionsQuantitative analysis of total plasma DNA and plasma APC/RASSF1A methylation provide a real-time synchronous rapid monitoring indicator for therapeutic outcomes of advanced lung cancer, which could be a reference or supplementary guidelines in evaluating chemotherapy effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0150-9) contains supplementary material, which is available to authorized users.
Highlights
The Response Evaluation Criteria in Solid Tumors (RECIST) guideline and Common Terminology Criteria for Adverse Events (CTCAE) criteria are used to assess chemotherapy efficiency and toxicity in patients with advanced lung cancer
The current Response Evaluation Criteria in Solid Tumors (RECIST) guideline, which is based on tumor size measured by chest X-ray or CT scan, and widely used tumor markers assay (such as carcinoembryonic antigen (CEA) and neuronal specific enolase (NSE)) are not sensitive enough to monitor chemotherapy effects in an individual patient because these markers require more than a month after chemotherapy to provide the information of
Methylation levels increased 24 h after cisplatin administration in A549 cells and in tumor-bearing nude mice To determine whether APC or RASSF1A gene promoters were methylated in A549 cells, we first assayed the methylation status of this cell line compared with H460 cells, which acted as a positive control
Summary
The Response Evaluation Criteria in Solid Tumors (RECIST) guideline and Common Terminology Criteria for Adverse Events (CTCAE) criteria are used to assess chemotherapy efficiency and toxicity in patients with advanced lung cancer. Total circulating DNA is at a low level—mainly from a few apoptotic normal cells (usually lymphocytes and other nucleated cells) [11] When both normal and tumor cells are killed by chemotherapy drugs, total circulating DNA will obviously increase; DNA from the normal cells will reflect the side effects of the drugs. Circulating tumor DNA with abnormal methylation patterns can be detected with a notable degree of specificity, even in the presence of excess DNA from normal cells This was the start point for the present study to use total circulating DNA and methylation assays as indicators of the efficacy of chemotherapy in ALC patients
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