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CLINICAL AND PATHOLOGIC OUTCOMES IN MSI-HIGH GASTROESOPHAGEAL CANCERS
Priya K. Pai
*, Mojun Zhu, Travis E. Grotz
Mayo Clinic Minnesota, Rochester, MN
BACKGROUND
Gastroesophageal cancers (GEC) with deficient mismatch repair proteins or high microsatellite instability (dMMR/MSI-H) are unique as they respond better to immune checkpoint inhibitors (ICI) than chemotherapy. Long-term outcomes of these patients, however, are lacking.
METHODS
This is a retrospective study that included patients with dMMR/MSI-H GEC who received treatment at our institution between 2000-2024. Descriptive statistics are reported as median and interquartile range (IQR).
RESULTS
Nineteen patients with dMMR GEC were identified. The median age at diagnosis is 68 years (IQR). The most common (89.47%) location of the cancer is distal stomach. Five patients (26%) underwent upfront R0 resection (disease ranging from Stage I-III at diagnosis): 3 received adjuvant chemoradiation, 1 received adjuvant chemotherapy and 1 did not receive adjuvant therapy. None developed recurrent cancer or died of cancer after a median follow up of 12 years. The other 14 patients received neoadjuvant-intent therapy. Among the 7 patients (50%) who received neoadjuvant chemotherapy and ICI, 6 (85.7%) had a complete response (CR) and 1 (14.3%) had partial response (PR) based on radiographic assessment. 2 patients with CR proceeded to surveillance and had no evidence of disease (NED) for 1 and 3 years, respectively. The patient with PR remains alive at 3 years with disease progression after discontinuing ICI due to adverse effects. 4 of the 6 patients with radiographic CR underwent R0 resection, of which 3 (75%) had a pathologic CR and 1 (25%) had a near pCR. All remain alive with NED after a median follow up of 2.5 years. Three (21.42%) patients received neoadjuvant chemotherapy only. None had a pCR and one of these patients died of metastatic disease. Two (14.28%) patients received neoadjuvant chemoradiation with 1 achieving pCR and the other no pathologic response. Both are alive after 1 (with recurrent disease), and 2 year (NED) follow up. 1 (7.14%) patient received chemotherapy, chemoradiation as well as ICI and was lost to follow up after disease continued to progress. The last patient (7.14%) had metastatic disease at diagnosis and opted for palliative care.
CONCLUSION
In this small study, patients with dMMR GEC who received upfront surgery or neoadjuvant ICI-containing therapy appear to have better outcomes. Larger studies are needed to determine the role and timing of surgery in dMMR GEC given favorable response to ICI-containing therapy.
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