Background Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs. Methods We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs. Results From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091). Conclusion In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.

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Gastric cancer (GC) represents one of the most fatal neoplasms in gastrointestinal oncology and affected patients can only hope for cure in limited disease. In a metastatic situation however, patients have a worse prognosis finally resulting in cancer-related death. Some improvements were made by using intensified chemotherapy such as the FLOT protocol (5-FU, leucovorin, oxaliplatin and docetaxel). However, a breakthrough in the treatment of advanced GC has been achieved by pre-therapeutical tumor analysis for potentially targetable alterations. Microsatellite instability, PD-L1 expression, Epstein Barr virus, and human epidermal growth factor receptor-2 (HER2) overexpression or amplification are the most beneficial targets, if addressed, can prolong survival in a palliative situation. Whether the combination of these targeted therapeutics with chemotherapy can bring long-term survival or even a chance of cure in a metastatic situation is not clear. Here, we report the case of a 30-year-old man with GC and extensive metastases who was cured by anti-HER2 antibody Trastuzumab combined with the FLOT regime. Initial staging showed an exophytic Siewert type III tumor and extensive hepatic metastases. Histology resulted in gastric adenocarcinoma with HER2 overexpression (2+, FISH positive). Twelve courses of chemotherapy comprising Trastuzumab and FLOT were administered. After treatment, the extensive liver metastases had disappeared with no evidence of residual tumor growth on the CT scans. Monotherapy of Trastuzumab was continued until gastrectomy with D2 lymph node dissection and probing of liver tissue, which revealed no residual tumor cells. Five years after surgery, there is continued complete remission. In conclusion, Trastuzumab in combination with FLOT may have curative potential even for metastatic stages of HER-2-positive GC.

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4116 Background: Immunotherapy based combinations recently revolutionized the treatment of patients (pts) with advanced HCC, but its significance in earlier stages remains to be determined. TACE is commonly used as first line treatment in intermediate HCC, but outcome of patients treated with TACE in real-life cohorts is still poor with a median overall survival (OS) below 20 months. The aim of this study was to determine the safety and efficacy of TACE combined with nivolumab. Methods: This is a phase II trial, that recruited 59 patients at 10 sites in Germany between 06/2018 and 06/2020. Pts received up to two TACE treatments followed by nivolumab (240 mg/ Q2W), initiated on day 2-3 after the first TACE session and continued until progression for a maximum treatment duration of two years. Primary endpoint was ORR (mRECIST; with ORR exceeding 55% (power = 80%; actual beta 0.17) as promising for further investigations). Secondary endpoints include mPFS, mTTFS (median time to failure of strategy), mOS, QoL, and safety/tolerability. Tumor tissue was obtained at baseline and blood samples were collected longitudinally for translational research. Results: 49 pts (14.3% HCV and 8.2% HBV) were enrolled and received at least one dose of nivolumab, median tumor size was 4.5 cm (0.9 – 15 cm) and median number 3 (1 – 12). ORR by mRECIST was 71.4% (CR: 16.3%, PR: 55.1%, SD 4.1%, PD: 14.3%). At a median follow-up of 20 months, mPFS was 7.2 mo (95% CI; 5.3 – 11.2; 40 events), mTTFS was 11.2 mo (95% CI; 7.2, 13.5; 42 events) and mTTSST (median time to subsequent systemic therapy) was 24.9 mo (95% CI; 12.2, - ; 21 events). Median duration of Nivolumab was 8.3 months and mOS was 28.3 mo (95% CI; 20 – not estimable; 23 events). Grade ≥3 treatment-related adverse events occurred in 34.7% of patients. Correlative analysis of efficacy with genetic alterations, gene expression signatures and changes of immune cell populations will be reported soon. Conclusions: The study met its primary endpoint and provides evidence for the efficacy of TACE in combination with nivolumab without new safety signals in pts with intermediate HCC and no prior systemic therapy. Our findings support further evaluation of nivolumab-based combinations for the treatment of intermediate HCC. Disclaimer: This study was supported with drug and funding by Bristol-Myers-Squibb. Clinical trial information: NCT03572582.