Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer.

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

Proposal of the Second Cutoff of Serum Carcinoembryonic Antigen Levels to Stratify Patients into Low, Intermediate, and High Risks at Recurrences after Curative Resection of Gastric Cancer.

INTRODUCTION: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 are widely used for treating various cancers, with cutoff values of 5.0 ng/mL and 37.0 IU/mL, respectively. However, these cutoff values are not for specific diseases or purposes but are uniformly used for any disease and any purpose. It is also unclear as to whether patients are at equal risk of recurrence if they are below the cutoff values. This study aimed to investigate the optimal cutoff of serum tumor markers in the stratification of recurrence risk after curative resection of gastric cancer. METHODS: We constructed a nine-center integrated database of patients who received gastrectomy between January 2010 and December 2014 with a 5-year follow-up period. We determined the cutoff value of preoperative serum tumor marker levels correlated with postoperative recurrences and evaluated its performance in risk stratification for recurrences in 948 patients with stage II/III gastric cancer who underwent radical resection. RESULTS: The hazard ratio for postoperative recurrences increased at two points of preoperative CEA levels, 3.6 ng/mL and 5.0 ng/mL, which were set as cutoffs. These two cutoffs stratified relapse-free survival into three levels. CONCLUSIONS: By adding a second cutoff value for preoperative serum CEA, which was proposed specifically for the prediction of recurrences, patients can be stratified into low-, intermediate-, and high-risk recurrences after curative resection of gastric cancer.

Significance of Preoperative Systemic Inflammation Score in Short-Term and Long-Term Outcomes of Patients with Pathological T2-4 Gastric Cancer After Radical Gastrectomy.

BACKGROUND: Surgical resection is the mainstay of treatment for patients with gastric cancer (GC). Development of a simple, high-performance, integrated scoring system is needed to provide appropriate management. This study aimed to evaluate predictive values of the systemic inflammation score (SIS) for short- and long-term outcomes of patients who underwent surgery for GC. METHODS: A total of 187 patients who underwent gastrectomy for pT2-4 GC without preoperative treatment were analyzed. SIS was formulated based on serum albumin level and lymphocyte-monocyte ratio, and graded into SIS 0, 1, and 2. RESULTS: Preoperative SIS was significantly associated with incidence of postoperative complications, showing a stepwise increased incidence in proportion to SIS in the entire cohort and all subgroups according to operative procedure and disease stage. Overall and disease-free survival times of patients in SIS 0, 1, and 2 shortened in a stepwise fashion. SIS was linked to prevalence of hematogenous metastasis as initial recurrence site. Survival differences between patients with SIS 2 and the others were particularly large in patients who underwent adjuvant chemotherapy. The continuation rate of adjuvant S-1 was lower in the SIS 2 group. CONCLUSION: SIS represents a simple predictor for incidence of postoperative complications and survival in patients with pT2-4 GC.

Mitochondrial sequence haplotype in the Japanese population.

Sequence polymorphysms of the mitochondrial DNA (mtDNA) control region, hypervariable regions I and II, from 50 unrelated Japanese were determined by PCR amplification and cycle sequencing.