Case Report: Complete Remission of a Patient With Metastatic Gastric Cancer Treated With Nivolumab Combined With Chemotherapy After Palliative Surgery

Abstract

Metastatic advanced gastric cancer, for which treatment strategies are extremely limited, has a poor prognosis. Complete remission is rare. Patients usually lose the opportunity of therapeutic surgery because the lesions cannot be completely removed, although it can greatly prolong their survival time. Palliative surgery usually suggests bad outcomes. In recent years, the immune checkpoint inhibitor (ICI) nivolumab has shown significant efficacy in the treatment of advanced gastric cancer. However, its applicable conditions and optimal withdrawal time remain controversial owing to its low response rate and high incidence of immune-related adverse events. Herein, we introduce a 66-year-old male patient with advanced gastric cancer with multiple liver metastases who underwent laparoscopic total gastrectomy for acute gastric bleeding. The patient received eight cycles of S-1 plus oxaliplatin (SOX) and switched to eight cycles of SOX plus nivolumab combined regimen in a stable state, later achieving complete remission. There was no recurrence for 32 months after the surgery. This is the first reported case of gastric cancer with multiple liver metastases with long-term complete remission with nivolumab treatment after palliative surgery. The potential mechanism of complete remission was discussed through clinical, genomic, and immune characteristics. The patient had a history of psoriasis and was positive for programmed death ligand 1 (PD-L1), and the interaction of TP53 mutation and HER-2 (-) gene may be associated with complete remission.

Keywords: advanced gastric cancer; case report; complete remission; immune checkpoint inhibitor; nivolumab.

Figure 1

According to an abdominal contrast-enhanced computed tomography (CT) scan, there were a malignant gastric mass and seven low-density shadows in the liver recognized as liver metastases (A). After eight cycles of SOX, contrast-enhanced CT scan showed no recurrence of the primary tumor, but liver metastases did not show any obvious changes (B). After surgery and chemotherapy for gastric cancer, the stomach was absent, and the lower esophagus and jejunum were anastomosed. A high-density metal anastomotic line shadow (indicated by the arrow) can be seen at the anastomotic stoma, and a small patch of slightly increased radiation uptake shadow can be seen locally. A small nodular low-density shadow with a size of about 0.5 cm can be seen in the right lobe of the liver (S8 segment). The density and radioactivity distribution in other parts of the liver were not abnormal. A small nodule-calcified shadow can be seen under the capsule of the right lobe of the liver (S6 segment). According to the positron emission tomography (PET) scan, the red arrows pointed out the tumor foci (C–E), the image (F) showed the image of coronal plane.

Figure 2

 A surgical intervention was implemented to remove the calcified liver metastasis (E) when pneumonia resolved, and PET (A–D) and CT scans (F) demonstrated that liver metastasis disappeared.

Figure 3

The course timeline showed that shortly after the diagnosis of advanced gastric cancer, the patient underwent total gastrectomy for acute gastric bleeding, followed by eight cycles of SOX and then eight cycles of SOX + nivolumab treatment. Subsequently, immune pneumonia occurred and was treated with methylprednisolone. After the patient became stable, the suspected calcified metastasis of the liver was removed, and all medications were stopped. The patient has achieved disease-free survival until now.

Figure 4

Multiplex immunofluorescence staining for CD8 (A), CD3 (B), PD-L1 (C), PD-1 (D), and the merged image (E) in the primary tumor tissue. The multiplex IHC platform, which can detect the expression of multiple markers in a single section, was utilized to measure the expression of PD- 1/PD-L1 and immune cell infiltration. The immune markers included CD8+ TIL and CD3+ TIL.