Total Neoadjuvant Therapy for Locally Advanced Gastric Cancer: An Interim Study of Phase II Clinical Trial.

Purpose/objective(s) To observe the safety and preliminary efficacy of the total neoadjuvant therapy (TNT) model of "neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy followed by radical surgery" for locally advanced gastric cancer (Clinical Trial registration number:NCT04062058). Materials/methods Patients aged 18-75 years with a KPS status score ≥70 and clinical diagnosed as locally advanced gastric adenocarcinoma (GC) or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer (GEJC) was prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45Gy,1.8Gy/time firstly. Concurrent chemotherapy was S-1 at a dose of 40-60mg twice daily. Then, patients received four to six cycles consolidation neoadjuvant chemotherapy (CNCT) of oxaliplatin and S-1(SOX regimen) three weeks after neoadjuvant chemoradiotherapy; R0 resection with D2 lymphadenectomy was performed 4-6 weeks after the end of neoadjuvant therapy. Results A total of 28 patients who finished the whole therapy were enrolled from March 2018 to December 2020, of which, 78.6% were diagnosed as cT4, 85.7% were cN positive and 85.7% were stage Ⅲ in total clinical stage. Grade 3 or higher adverse reactions occurred in 3 cases (10.7%) during CRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7.4%) of leukopenia and 3 cases (11.1%) of thrombocytopenia occurred during CNCT. Twenty patients (71.4%) completed surgery among 28 patients and all of them completed R0 resection. The incidence of severe pathological reactions (Mandard score = 1-2) was 95.0% and 50.0% reached pCR. Three patients occurred surgery complications, including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. They all improved after symptomatic treatment. Conclusion Total neoadjuvant therapy for locally advanced GC and GEJC can reach a remarkable down-staging. It can be safely delivered and will not improve the surgery complications significantly.