Abstract
Gastrointestinal cancers, including oesophageal, gastric and colorectal cancers (CRC) have high rates of disease recurrence despite curative resection. There are a number of recent studies that have investigated the use of circulating tumor DNA (ctDNA) for prognostic value in these cancers. We reviewed studies that had been published prior to March 2018 that assessed the prognostic values of ctDNA in patients with oesophageal and gastric cancers, gastrointestinal stromal tumors (GIST) and CRC. We identified 63 eligible clinical studies that focussed on recurrence and survival. Studies assessed investigated various ctDNA biomarkers in patients with different stages of cancer undergoing surgical resection, chemotherapy and no treatment. For oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, methylation of certain genes such as APC and DAPK have been highlighted as promising biomarkers for prognostication, but these studies are limited and more comprehensive research is needed. Studies focusing on gastric cancer patients showed that methylation of ctDNA in SOX17 and APC were independently associated with poor survival. Two studies demonstrated an association between ctDNA and recurrence and survival in GIST patients, but more studies are needed for this type of gastrointestinal cancer. A large proportion of the literature was on CRC which identified both somatic mutations and DNA methylation biomarkers to determine prognosis. ctDNA biomarkers that identified somatic mutations were more effective if they were personalized based on mutations found in the primary tumor tissue, but ctDNA methylation studies identified various biomarkers that predicted increased risk of recurrence, poor disease free survival and overall survival. While the use of non-invasive ctDNA biomarkers for prognosis is promising, larger studies are needed to validate the clinical utility for optimizing treatment and surveillance strategies to reduce mortality from gastrointestinal cancers.
Highlights
Gastrointestinal cancers, in particular gastric and colorectal cancer (CRC), have high incidence and mortality rate
While plasma EBV DNA may useful for monitoring clinical load in patients with EBV-associated gastric carcinomas, no significant difference was found between prognosis of recurrence-free survival of those with high pre-operative EBV copy numbers compared to those with low levels [67]
In two different studies of 38 primary CRC patients, Czeiger and colleagues found that pre-operative DNA level was a better indicator of prognosis than TNM staging for both disease-free survival (HR 6.03) and overall survival (HR 3.53) for all cancer stages
Summary
Gastrointestinal cancers, in particular gastric (stomach) and colorectal cancer (CRC), have high incidence and mortality rate. The following sections of this review will describe the studies that have been performed in gastrointestinal cancers to assess the utility of ctDNA for their prognostic value, whether measured as cfDNA concentration, integrity (fragment lengths), copy number alterations, mutation or methylation status. Eisenberger et al assessed loss of heterozygosity (LOH) in pre-operative ctDNA of SCC (n = 28) and oesophageal adenocarcinoma (n = 32) patients of all stages in two separate studies In both types of cancers, no relationship was found between recurrence and LOH; in SCC a trend toward shorter survival was observed for patients with LOH in tumor tissue and ctDNA [58, 59].
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