Locally advanced gastroesophageal junction cancer with pathological complete response to neoadjuvant therapy: a case report and literature review

Abstract

Most gastric cancer and gastroesophageal junction carcinoma (GEJ) patients are already in the advanced stage at the time of diagnosis. Thus, the probability of radical gastrectomy is low, and surgical treatment alone has a poor prognosis due to the high recurrence rate. In order to reduce the recurrence and distant metastasis after surgery, there have been many attempts made to improve the perioperative treatment of advanced localized gastric cancer, but no uniform criteria exist. Over recent years, immunotherapy has revolutionized cancer treatment, and immune checkpoint inhibitors (ICIs) have shown excellent efficacy across various types of tumors, becoming a potential treatment after surgery, chemotherapy, radiotherapy, and targeted therapy. However, the efficacy of single-agent ICIs for gastric cancer is still unsatisfactory. As comprehensive, chemotherapy-based treatment has become the standard care for locally advanced gastric cancer, exploring combination treatment with immune checkpoint inhibitors (ICIs) may be valuable to improving survival outcomes. Here, we report a 66-year-old male with dysphagia diagnosed with GEJ and was defined as clinical stage (cT4N2M0) and Siewert type II, characterized as mismatch repair proficient (pMMR) and programmed cell death ligand-1 (PD-L1) negative; surprisingly, with anti-PD-1 antibody plus SOX (S-1: a combination of tegafur, gimeracil, and oteracil+ oxaliplatin) as perioperative therapy, the patient achieved pathological complete remission (pCR), which indicates that the addition of ICIs to chemotherapy as a perioperative comprehensive treatment might provide a promising strategy option for GEJ. In addition, we review the current status of perioperative comprehensive treatment, in hope that this may provide some reference value for clinical decision-making.

Keywords: Case report; PD-1; gastric and gastroesophageal junction cancer; neoadjuvant therapy.

Figure 1

Computed tomography scan of the tumors and regional lymph nodes (blue arrows) before and after anti-PD-1 therapy combined with chemotherapy as well as after surgery. Computed tomography images of primary lesions and regional lymph nodes before (A,B,C) and after (E,F,G) combined immunotherapy and chemotherapy, and after surgery (H,I,J). Primary tumor and metastatic lymph nodes are no longer visible after immune-chemotherapy. Gastroscopy revealed a mass adjacent to the cardia before neoadjuvant therapy (D).

Figure 2

Immunohistochemistry of mismatch repair proteins. The tumor cells are positive for MLH1 (A), MSH2 (B), PMS2 (C), and MSH6 (D). Scale bar: 50 µm Original magnification: 400×.

Figure 3

Immunohistochemistry assay of PD-L1 protein and EBV status. PD-L1 (B7-H1) was negative in tumor tissue by immunohistochemistry assay (A) and EBV virus was absent by using EBV-encode small RNA (EBERs) in situ hybridization (B). Scale bar: 50 µm. Original magnification: 400×.

Figure 4

The histopathology of the primary tumor specimens and the immunohistochemistry of the primary tumor biopsy specimens as well as postoperative pathology. Hematoxylin and eosin (HE) staining of tumor specimens before surgery (A). Postoperative pathology showed no residual tumor cells, and a pathological complete response was achieved (B). CD3+ tumor-infiltrating lymphocytes were observed, with a tumor proportion score (TPS) of around 20%. (C) CD8+ tumor-infiltrating lymphocytes had a TPS of about 1% (D). The CD45RO+ tumor-infiltrating lymphocytes TPS score was about 15% (E). FOXP3 tumor-infiltrating lymphocytes was not observed (F). Scale bar: 50 µm. Magnification: 400×.

Figure 5

Timeline of diagnosis and treatment.