Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Ann Surg Oncol. 2024 Dec;31(13):8616-8626. doi: 10.1245/s10434-024-16030-0. Epub 2024 Aug 17.
Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI).
Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages.
A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient.
dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.
错配修复缺陷（dMMR）胃食管癌症（GEC）是一个独特的亚组。在局部晚期疾病患者中，先前的试验数据表明对新辅助免疫检查点抑制剂（nICI）有良好的反应。
自 2019 年以来，我们机构已常规对新 GEC 病例进行 MMR 检测。纳入本研究的患者诊断为 GEC（2019-2024 年）。定量数据以中位数和四分位距（IQR）表示；定性数据以数量和百分比表示。
实施常规免疫组织化学检测后，共确定 24 例 dMMR GEC 患者；中位随访 14 个月（IQR 8-27），14 例可能可切除。所有患者均行治疗前正电子发射断层扫描（PET；中位 SUV20.9）。在 14 例潜在可切除患者中，4 例立即行手术，10 例行 nICI 治疗，5 例迄今行手术切除。所有方案均包括 PD-1 抑制剂，70%接受 pembrolizumab 治疗。对 5 例患者行再分期 PET；nICI 后中位 SUV 为 5.1（范围 4.7-6.3）。nICI 后所有切除标本均有大体溃疡，但 60%（N=3）的患者有病理完全缓解（pCR）；1 例患者有接近完全缓解（nCR），1 例患者有部分缓解（pPR）。pCR 患者 SUV 降低 75%和 82%，nCR 患者降低 25%，pPR 患者降低 43%。
在这一有限的经验中，dMMR GEC 对 nICI 有反应，与早期临床试验数据一致。鉴于尽管有 pCR 但仍存在持续的代谢活性和可见的溃疡，应继续开展研究以优化这些患者 nICI 后 pCR 的评估工具。
