Survival outcomes in patients with resectable gastric cancer treated with total neoadjuvant therapy.

Abstract

338 Background: Perioperative chemotherapy is the standard of care for patients diagnosed with advanced gastric cancer. However, the use of total neoadjuvant therapy (TNT), which includes both chemotherapy and chemoradiation, is increasing in other malignancies. The purpose of this study is to determine overall survival (OS) in a contemporary cohort of gastric cancer patients treated with TNT and surgical resection. Methods: Patients diagnosed with microsatellite-stable clinical T2+ or N+ gastric adenocarcinoma (January 2012 to June 2022) were identified from a prospectively maintained institutional database. Those who underwent staging laparoscopy and received neoadjuvant chemotherapy and chemoradiation therapy, followed by gastrectomy, were included in the study. OS and variables associated with OS were determined using standard statistical methods. Results: Of 203 study patients, the median (interquartile range) age was 61 (50-69.5) years and 50 (24.6%) had tumor involving the gastroesophageal junction. The most common TNT sequence was chemotherapy followed by chemoradiation, which was utilized in 173 (85.2%) patients. The chemotherapy regimen typically given was fluorouracil and oxaliplatin in 149 (73.4%) patients. The most common radiation dose was 45 Gy in 25 fractions (169 [83.3%] patients), with 18 (8.9%) patients receiving 30 Gy in 10 fractions. One hundred ninety-seven (97.0%) patients completed all their planned neoadjuvant therapy. Surgical resection included total gastrectomy in 108 (53.2%), adjacent organ resection in 24 (11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4 (95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2% (95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82]; ypT4 vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13]; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6]), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]), and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS. Conclusions: TNT is associated with a high rate of treatment completion and promising long-term OS for patients with resectable gastric cancer. Comparative studies with perioperative treatment and predictors of tumor response will be important in identifying patients suitable for TNT.