Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports

Abstract

Background: Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response.

Case presentation: In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells.

Conclusions: We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.

Keywords: Complete response; Conversion surgery; Gastric cancer; Liver metastases; Nivolumab.

Fig. 1

Case 1. a Treatment course in Case 1. The patient was diagnosed with advanced gastric cancer and multiple liver metastases (yellow arrowheads) and received SOX plus nivolumab therapy. After 13 cycles of chemotherapy, all liver metastases except those in S3 and S4 were resolved, and the primary lesion was remarkably reduced. MRI showed two remaining liver metastases measuring 5 mm in segment 4 and 3 mm in segment 3 (yellow dashed lines). The patient developed sinus occlusion syndrome caused by oxaliplatin and received three additional cycles of nivolumab monotherapy. The primary lesion slightly increased in size, but the liver metastases remained at a reduced size. The patient thereafter underwent conversion surgery. b A Borrmann type 3 tumor was found in the gastric antecubital area, and the pyloric ring was deformed. c A white scar was visible on the surface (green arrowheads). d The resected liver tissue had transformed into fibrous tissue devoid of malignancies. EGD esophagogastroduodenoscopy, CT computed tomography, MRI magnetic resonance imaging

Fig. 2

Case 2. a Treatment course in Case 2. The patient was diagnosed with advanced gastric cancer and multiple liver metastases and received SOX therapy. The primary lesion shrank (yellow arrowheads) and the liver metastases disappeared soon after the start of treatment. Twenty-one months after starting SOX therapy, the patient was switched to ramucirumab plus paclitaxel therapy because of the appearance of new liver metastases (green arrowheads). Only one cycle of ramucirumab plus paclitaxel therapy was completed because of severe neutropenia, and the patient was then started on nivolumab therapy. Eight months after nivolumab therapy, contrast-enhanced magnetic resonance imaging showed necrosis of the liver metastasis (pink arrowhead). However, the primary lesion continued to grow. Consequently, the patient underwent conversion surgery. b A Borrmann type 1 tumor was found on the fornix. c White nodules on the cross-section of the liver (white arrowheads). d Viable atypical cells disappeared from all specimens. The same area showed fibrosis and edema. RAM ramucirumab, PLX paclitaxel, EGD esophagogastroduodenoscopy, CT computed tomography, MRI magnetic resonance imaging

Fig. 3

Case 3. a Treatment course in Case 3. The patient was diagnosed with advanced gastric cancer, multiple liver metastases (yellow arrowheads), and multiple para-aortic lymph node (PALN) metastases (yellow dashed lines) and received SOX plus nivolumab therapy. After 10 cycles of chemotherapy, all liver metastases (except those in S7) and the PALN metastases were resolved (green arrowhead and dashed lines), and the primary lesion was remarkably reduced. The patient developed sinus occlusion syndrome caused by oxaliplatin and received five additional cycles of nivolumab monotherapy. The primary lesion increased in size, but the liver metastasis and the PALN metastases were maintained at a reduced size. The patient thereafter underwent conversion surgery. b A Borrmann type 3 tumor with two ulcers in the gastric lesser curvature and anterior wall. c White nodules in the liver. d Viable atypical cells disappeared from all specimens. The site contained an inflammatory cell infiltrate and some fibrosis. EGD esophagogastroduodenoscopy, CT computed tomography, MRI magnetic resonance imaging