Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient

Abstract

Background: Immuno-oncology is a novel target of cancer therapy. Nivolumab is a monoclonal anti-programed death-1 antibody recently used to treat patients with chemotherapy-resistant gastric and gastroesophageal cancer. Although the disease control rate is reported to be very high, few cases demonstrate a complete response. Case Presentation: A 25-year-old man diagnosed with gastroesophageal cancer was treated with chemotherapy followed by surgical resection. Pathological diagnosis was poorly differentiated adenocarcinoma with distant lymph node metastasis. Residual lymph node metastasis was treated with nivolumab monotherapy, resulting in complete disappearance. No recurrence has been observed for 2 years since discontinuation of nivolumab. This rare case was additionally subjected to pathological and genetic analysis, suggesting that a high tumor mutation burden (10.7 mutations/Mb) might be associated with sensitivity to nivolumab. Summary: We reported a case of advanced gastroesophageal junction cancer with distal lymph node metastasis that was successfully treated with chemotherapy, surgical resection, and nivolumab therapy. An aggressive search for biomarkers implying benefit effects of nivolumab should be performed.

Keywords: complete remission (CR); gastric cancer; immunotherapy; lymph node metastasis (LNM); tumor burden.

Figure 1

Upper gastrointestinal endoscopic images and histological analyses of the gastroesophageal junction cancer. (A) Deep ulceration with a rounded bank was observed in the junction. (B) Swelling of the gastric fold indicated submucosal invasion of the cancer cells in the cardia of the stomach. (C) H&E staining of the biopsy specimen showed poorly differentiated adenocarcinoma. (D) Immunohistochemistry revealed that gastric cancer cells were positive for human epidermal growth factor 2 (HER2). (E) An SP142 assay revealed that both cancer cells and stromal cells were negative for programmed death-1 ligand 1. (C–E original magnification ×200).

Figure 2

Images of computed tomography before (A,B) and after (C,D) chemotherapy. (A) Cardiac wall thickness and connected lymph node swelling was observed. (B) Paraaortic lymph node metastasis (#16) showed distant metastasis of 30 mm in size (indicated by a red arrow). (C) The lymph node of the gastric cardia had shrunk. (D) The paraaortic lymph node metastasis (#16) had shurunk to 19 mm in size (a blue arrow), showing a partial response.

Figure 3

Changes in tumor markers during the course of the treatment. CEA and AFP sharply decreased after chemotherapy but re-elevated after three cycles. Surgery failed to reduce CEA, but nivolumab was effective. Tumor markers remained in their normal ranges after discontinuation of all treatment. HXP, Herceptine, Xeloda, and Cisplatin; Nivo, nivolumab; CT, computed tomography.

Figure 4

Images of computed tomography 1 month after surgery (A–C) and after finish of the nivolumab threatment (D–F). Lymph node metastasis was observed (A) in the subclavicle (#104L, yellow arrowhead), (B) mediastinum (#108L, yellow arrow), and (C) paraaorta (#16b1, red arrow), indicating distally metastatic recurrence of the carcinoma (progressive disease). Lymph node metastasis of (D) the subclavicle (#104L), (E) mediastinum (#108L), and (F) paraaorta (#16b1) had vanished, indicating a complete response.