RESUMO
Hepatoid adenocarcinoma of the stomach is an uncommon subtype of gastric cancer remarkably similar to hepatocellular carcinoma in histopathological analysis. It is also commonly associated with high serum alfa-fetoprotein and a poorer prognosis, despite the emergence of new therapeutic options. In recent years, next generation sequencing (NGS) technology has made it possible to identify and describe the genes and molecular alterations common to gastric cancer thereby contributing to the advancement of targeted therapies. A 62-year-old patient, with no prior risk factor for hepatocellular carcinoma (HCC), presented to the emergency room with dysphagia for solids, abdominal pain and weight loss of about 3 kilograms over 3 months. Histopathological analysis presented with disparities regarding HER2 and programmed death-ligand 1 (PD-L1) status in the primary and metastatic sites. We describe a case of a de novo metastatic, human epidermal growth factor receptor 2 (HER2) positive esophagogastric junction hepatoid adenocarcinoma. Although this is a rare subgroup of gastric cancer, treatment strategies were based in recent studies in immunotherapy and guided therapy, taking into consideration the molecular findings from the patient's tumor NGS analysis. Data about HER2 and PDL1 heterogeneity were also reviewed. Despite the aggressiveness and rarity of this histology, the patient had a good response to treatment.
RESUMO
Esophageal carcinoma is an aggressive malignancy and outcomes remain poor. Immune checkpoint inhibitors are a standard-of-care in the third-line and beyond settings, although benefit is modest. Herein, we report the case of a patient who achieved a partial response to salvage chemotherapy following treatment with an immune checkpoint inhibitor despite having chemo-refractory disease. A 41-year-old male, with a history of Crohn's disease, was diagnosed with Her2-positive metastatic esophageal adenocarcinoma to lungs and lymph nodes. The patient received multiple lines of systemic therapy including: first-line modified DCF (docetaxel/cisplatin/5-fluorouracil) with trastuzumab, second-line trastuzumab/afatinib on a clinical study, third-line carboplatin/irinotecan/ramucirumab and fourth-line treatment with a Her2 antibody-drug conjugate, DS-8201A, on a phase I study. While the patient was not a candidate for clinical trials evaluating immune checkpoint inhibitors due to his history of Crohn's disease, the latter was well controlled. Thus, the patient commenced pembrolizumab as fifth-line of treatment 2 years since diagnosis. After 3 cycles of therapy, the patient developed grade 3 immune-related colitis and treatment was discontinued. The patient maintained a good performance status and commenced a sixth-line of carboplatin/irinotecan/ramucirumab. Subsequent imaging demonstrated a partial response which was maintained over a 6-month period. This case demonstrates a response to previously administered chemotherapy following immune checkpoint inhibitor therapy, despite prior progression on this chemotherapy regimen. To our knowledge, this has not been previously reported in esophagogastric carcinoma (EGC). Post-immune checkpoint inhibitor chemotherapy may be a feasible treatment strategy. Research is needed to evaluate the role of post-immune checkpoint inhibitor chemotherapy in patients with metastatic EGC.