This study focused on comparing neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) with surgery and/or chemotherapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) resectable gastroesophageal adenocarcinoma (GEA). These tumors are known to respond poorly to chemotherapy but are highly immunogenic, making immunotherapy a promising approach.
This study focused on comparing neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) with surgery and/or chemotherapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) resectable gastroesophageal adenocarcinoma (GEA). These tumors are known to respond poorly to chemotherapy but are highly immunogenic, making immunotherapy a promising approach.
The analysis included 197 patients divided into four groups: ICIs (49 patients), FLOT chemotherapy (27 patients), surgery alone (33 patients), and older chemotherapy regimens (88 patients). The study primarily assessed pathologic complete response (pCR) and major pathologic response (MPR) rates, alongside event-free survival (EFS) and overall survival (OS).
Key findings showed that neoadjuvant ICIs resulted in significantly better tumor responses compared to chemotherapy. Patients treated with ICIs achieved a pCR rate of 61.9% versus 3.7% with FLOT chemotherapy, and an MPR rate of 78.6% versus 10%. Additionally, ICIs reduced residual nodal disease (ypN+) to 14.3% compared to 37% with chemotherapy, indicating superior tumor downstaging.
Despite these impressive pathologic responses, survival outcomes (EFS and OS) were comparable between ICIs and surgery ± chemotherapy groups. At 36 months, EFS was 70.4% for ICIs versus 80.6% for surgery, and OS was 72.7% versus 90.4%. Patients with residual nodal disease (ypN+), advanced tumor stage (ypT4), or lack of pathologic response had worse survival outcomes.
This study highlights neoadjuvant immunotherapy as a highly effective strategy for dMMR/MSI-H GEA, offering profound tumor regression and reduced reliance on chemotherapy. These findings support the potential for organ-sparing or non-surgical treatment approaches, paving the way for immunotherapy-centered management in this patient subgroup.
Introduction: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring treatment response and residual disease in solid tumors. However, its prognostic value during neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma...
Introduction: Aspirin is one of the few interventions proven to reduce colorectal and other Lynch syndrome–associated cancers. The earlier CaPP2 trial established 600 mg daily aspirin as an effective chemopreventive strategy, but concerns regarding long-term...
Introduction: The TOPAZ-1 trial established durvalumab combined with gemcitabine and cisplatin (GemCis) as the first immunotherapy-based first-line standard of care for advanced biliary tract cancer (BTC). However, long-term survival outcomes and durability of benefit beyond...
Introduction: Somatostatin receptor (SSTR) PET/CT has become indispensable for diagnosing, staging, and monitoring neuroendocrine tumors (NETs). However, until now, there has been no standardized method for assessing treatment response using SSTR PET imaging. This international...
Introduction: Staging laparoscopy (SL) is recommended for patients with locally advanced gastric cancer to detect occult peritoneal metastases before curative treatment. However, its real-world utilization across Europe remains uncertain. This large GASTRODATA study evaluated the...
Introduction: Neoadjuvant immune checkpoint inhibitors have transformed the management of mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer, achieving unprecedented pathological response rates. Experimental evidence suggests that cyclooxygenase-2 (COX-2) inhibition may enhance...
We are pioneers in clinical intelligence, dedicated to helping gastroenterologists harness the power of artificial intelligence to drive precision, efficiency, and patient growth.