A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II - III gastric cancer patients

Abstract

Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients.

Methods: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed.

Results: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests.

Conclusions: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Keywords: Prognostic test; adjuvant chemotherapy; advanced gastric cancer; feasibility; gastrectomy.

Figure 1

SPC algorithm and a flowchart of the study. (A) SPC categorizes stage II−III gastric cancer patients into immune/stem cell/epithelial subtypes, effectively differentiating patients into three distinct risk groups (low, intermediate, and high) with varying survival rates. To be more specific, the low-risk group was identified by the high expression of immune genes, GZMB and WARS, with cut-off values of −5.18 and −2.14, respectively. Meanwhile, the intermediate and high-risk groups were differentiated by the expression of the stem-like gene SFRP4, where the high-risk group exhibited a high level of SFRP4 with a cut-off value of −3.63; (B) This study evaluated the feasibility of SPC test in a clinical setting. When the FFPE specimen slides of the enrolled patients were prepared, they were transported to the laboratory for analysis with nProfiler® 1 Stomach Cancer Assay. The results were reported back to the test referred hospital. We defined the cases with “timely delivery”, when the SPC test results were delivered back to the test referred hospitals before the treatment decision is made to patients following gastrectomy. The primary endpoint of this study is the proportion of cases with “timely delivery” of test results. The secondary endpoint is 3-year DFS of the enrolled patients. SPC, single patient classifier; FFPE, formalin-fixed, paraffin-embedded; DFS, disease-free survival; QC, quality control.

Figure 2

A flow diagram of patient selection through the study. AJCC, American Joint Committee on Cancer.

Figure 3

Kaplan-Meier survival curves according to stage (P=0.003) (A), prognostic group (P=0.021) (B), prognostic group in stage II (P=0.053) (C) and stage III (P=0.310) (D) subgroups in the full analysis set. LR, low risk; IR, intermediate risk; HR, high risk.

Figure S1

Stratified analysis by sex. (A) Female (n=75) (P=0.24); (B) Male (n=153) (P=0.10).