Total neoadjuvant therapy for locally advanced gastric cancer and esophagogastric junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase II clinical trial

Abstract

Background Gastric cancer ranks high in terms of morbidity and mortality worldwide. Multimodal therapy is therefore essential for locally advanced gastric cancer. Recent studies have demonstrated that both perioperative chemotherapy and neoadjuvant chemoradiotherapy can improve the prognosis of patients. However, the completion rate of chemotherapy after surgery remains low, which may affect survival. Thus, identifying the best way to combine radiotherapy, chemotherapy and surgery is important. The aim of this study was to explore the toxicity and efficacy of the total neoadjuvant therapy modality for locally advanced gastric cancer. Methods This study will be a prospective, multicenter, single-arm, phase II clinical trial. Patients diagnosed with locally advanced (stage cT3-4 and cN positive, AJCC 8th) gastric cancer and gastroesophageal junction adenocarcinoma will be enrolled. Patients will initially receive radiotherapy (95% planned target volume: 45 Gy/25 f) and concurrent chemotherapy (S-1: 40–60 mg twice a day) followed by six cycles of consolidated chemotherapy (SOX, consisting of S-1 and oxaliplatin) and surgery. The primary objective will assess pathological complete response; the secondary objectives will include toxicities assessing surgical complications, the tumor downstaging rate and the R0 resection rate. Discussion Investigation of total neoadjuvant therapy in gastric cancer is limited. The goal of this trial is to explore the efficacy and toxicity of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma. Trial registration: Clinicaltrials.gov (NCT04062058, August 20, 2019).

The inaccuracies of gastric adenocarcinoma clinical staging and its predictive factors

“…In addition, clinical staging provides significant value to clinicians in terms of patient prognostication, which can often directly affect care as well as patient expectations of disease 4,17,18 . While the standard of care for patients with stage I gastric cancers is generally upfront surgical resection, a more individualized approach for patients who present with stage II–III disease is generally undertaken, as these patients have been shown to benefit from perioperative systemic therapy 19–21 . Given the results of key landmark trials, 19,22,23 in general, there has been a shift to a neoadjuvant approach to chemotherapy for patients who present with stage II–III gastric cancer 4 .…”

“…4,17,18 While the standard of care for patients with stage I gastric cancers is generally upfront surgical resection, a more individualized approach for patients who present with stage II-III disease is generally undertaken, as these patients have been shown to benefit from perioperative systemic therapy. [19][20][21] Given the results of key landmark trials, 19,22,23 in general, there has been a shift to a neoadjuvant approach to chemotherapy for patients who present with stage II-III gastric cancer. 4 However, alterations in treatment strategy selection vary based on individual patient characteristics leading to a significant portion of patients who still undergo upfront curative-intent gastrectomy.…”

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

“…Patients will initially receive radiotherapy and concurrent S-1 chemotherapy, followed by six cycles of combined SOX chemotherapy and surgery. The primary objective will be to assess the pathological complete response; secondary objectives will include the assessment of toxicity, surgical complications, the tumor downstaging rate and the R0 resection rate [40].…”

Total neoadjuvant therapy for locally advanced gastric cancer: too much of a good thing?

“…Here, innovative trial designs of TNT approaches incorporating radiation and novel systemic therapies including targeted therapies and immunotherapies seek to build on existing standard therapies to improve efficacy in an adaptive design with evolving arms, while implementing adaptive treatment strategies in response to neoadjuvant therapy-based tumor response criteria into the study design ( 10 , 11 ). Trials are ongoing to assess the incorporation of radiation with a consolidated chemotherapy regimen to assess the rate of pCR following TNT ( 12 ). There is also compelling retrospective and phase I/II data on perioperative chemoradiation therapy (CRT) for GC, though this has not been confirmed in randomized phase II trials ( 13 ).…”