Abstract
Background Circulating tumor DNA (ctDNA) derived from tumors is a promising biomarker for monitoring tumor status and evaluating therapeutic effects and prognosis. We studied the plasma human epidermal growth factor receptor 2 (HER2) amplification in gastric cancer (GC) patients by droplet digital PCR (ddPCR) during therapy with trastuzumab. Methods A total of 12 patients were recruited after surgery. All patients received FOLFOX chemotherapy combined with trastuzumab as a treatment regimen. During the 12 months of the follow-up period, using elongation factor Tu GTP binding domain containing 2 (EFTUD2) as a reference gene, plasma HER2 to EFTUD2 ratios (the HER2 ratio) were determined for each patient every 2 months by ddPCR. Results The concordance rate of HER2 amplification examined in plasma and formalin-fixed paraffin-embedded (FFPE) samples with ddPCR was 81.4%, with a sensitivity of 76.5% and a specificity of 83.8%. Plasma HER2 ratios were correlated with the primary tumor size (p < 0.01). A significant decrease in the plasma HER2 ratio was found after two months of treatment (p < 0.0001). Nine patients experienced partial response, and three patients had stable disease. Seven patients had progressive disease (PD) during follow-up, and four of them had died. The median progression-free survival (PFS) was 9.8 months. For each patient who developed PD, the plasma HER2 ratio was approximately 2.3-4.1 times higher than the cut-off value at the time of PD, which was the highest during the whole follow-up period. Conclusion Longitudinal monitoring for the plasma HER2 ratio by ddPCR in the clinical courses of GC patients holds great promise for use as an indicator of tumor progression and treatment efficacy.
Highlights
According to the latest cancer statistics, gastric cancer (GC) is the second most common cancer in terms of incidence and mortality in China [1]
Enrollment criteria included the following: (1) patients were categorized as stage III or IV according to TNM stage classification, (2) patients received treatment with trastuzumab, (3) patients’ tumor biopsies and blood samples were human epidermal growth factor receptor 2 (HER2) positive as detected by droplet digital PCR (ddPCR), and (4) by a signed agreement, patients agreed to provide additional blood samples and received clinical examination including computed tomography (CT) imaging every 2 months during the 12 months of follow-up
A total of 12 patients with advanced GC were enrolled in the present study, comprised of 7 males and 5 females
Summary
According to the latest cancer statistics, gastric cancer (GC) is the second most common cancer in terms of incidence and mortality in China [1]. The results were mostly not promising, two meta-analyses of randomized trials revealed that HER2 was the most effective of targeted drugs for its outstanding improvement of OS and progression-free survival (PFS) [10, 11]. A regular monitoring of the HER2 status to evaluate the prognosis and reconsider treatment strategies was potentially required, but clinical monitoring of molecular mutations or changes in expression through repeated biopsy of tumor tissues would be difficult, because of its invasive nature, high incidence of inducing tumor metastasize, and so on. We studied the plasma human epidermal growth factor receptor 2 (HER2) amplification in gastric cancer (GC) patients by droplet digital PCR (ddPCR) during therapy with trastuzumab. Longitudinal monitoring for the plasma HER2 ratio by ddPCR in the clinical courses of GC patients holds great promise for use as an indicator of tumor progression and treatment efficacy
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