PMC9773983_01
Imaging taken at baseline before initiation of treatment. (A, B) Gastroscopy illustrated lower esophagus, cardia and cardia by lumen narrowing. There is a huge ulcer in the cardia. The nodules at the bottom are uneven and covered with dirt moss. (C) Hemotoxylin and eosin (H&E): cardia with poorly differentiated adenocarcinoma (H&E, x100 original magnification). (D-F) Computed tomography (CT) taken at the primary GEJ cancer and liver metastasis, lung metastasis and multiple lymph node metastasis.
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B ). Biopsy pathology: poorly differentiated adenocarcinoma ( Figure 1C ). Contrast-enhanced Computed tomography (CT) of the cervicothoracic abdomen and pelvis demonstrated: cardiac cancer involving the esophagus and lesser curvature of stomach, with multiple lymph node metastasis; superior lobe metastasis of the left lung; hepatic metastasis ( Figures 1D-F ). The results indicated that TP53, JAK3, JARID2, CDKN2C, GREM1, EMSY, ERBB2 mutations; copy number 58.4934 (ERBB2), 15.158 (CCNE1); structural variation (ERBB2, CDK12); tumor mutational burden (TMB) = 3.1, microsatellite stability (MSS) ( Figure 4A ,  Supplementary Figure S1 ).
Adverse reactions that occurred during treatment. (A) CT taken at multiple floc and patchy high-density shadows in both lungs, appearance of interstitial pneumonia. (B) CT taken at the pneumonia was better than before, and the lung metastatic lesions continued PR. (C) Immune-related hepatitis occurred in the patient during immunotherapy combined with single-drug capecitabine therapy. After combined steroid therapy with mycophenolate mofetil, the patient's immune hepatitis improved. The patient did not receive subsequent immune antitumor therapy, and immune-related hepatitis still occurred intermittently.
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Chest CT: multiple floc and patchy high-density shadows in both lungs, appearance of interstitial pneumonia ( Figure 2A ). A CT scan performed on 28 December 2020 showed that the pneumonia was better than before, and the lung metastatic lesions continued PR ( Figure 2B ). During the CT evaluation, his condition was sustained at PR on 2 September 2021 monitoring of liver function: ALT 173.7 U/L and AST 148.4 U/L ( Figure 2C ).
Complete response (CR) was confirmed by PET/CT and the biopsy specimen from gastroscopy. (A-E) 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging shows the best overall response of CR to treatment with AK104. FDG-avidity was abolished in the gastroesophageal junction, liver, lung, and multiple lymph nodes. (F-H) Gastroscopy showed that the dentate line was seen 40 cm away from the incisor, and the mucosa was slightly rough without stenosis, which was biopsied at 12 o'clock. (I). H&E: There was infiltration of inflammatory cells in the superficial layer of the cardia mucosa, while the glands in the deep layer were normal and no cancer cells were found (H&E, x100 original magnification).
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CR was confirmed by FDG-PET and the biopsy specimen from gastroscopy on 10 June 2020 ( Figures 3A-I ).
At the latest follow-up, next-generation sequencing (NGS) and immunohistochemistry (IHC) were performed on the patients' first biopsy tissue. (A) NGS-Geneseeq PRIME (425-Cancer Gene Panel) of biopsy tissue to guide subsequent therapy at a recent follow-up visit. The results indicated that TP53, JAK3, JARID2, CDKN2C, GREM1, EMSY, ERBB2 mutations; copy number 58.4934 (HER-2), 15.158 (CCNE1); structural variation (SV) ERBB2, CDK12; tumor mutational burden (TMB) = 3.1, microsatellite stability (MSS). (B-D) IHC: EBV (-), PD-L1 Combined Positive Score, CPS = 3 (PD-L1,22C3), HER-2 (3+) (x100 original magnification). *At position 55, base G changes to T, causing a codon that should have been translated to E(glutamic acid) to become a stop codon, resulting in translation termination.
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The results indicated that TP53, JAK3, JARID2, CDKN2C, GREM1, EMSY, ERBB2 mutations; copy number 58.4934 (ERBB2), 15.158 (CCNE1); structural variation (ERBB2, CDK12); tumor mutational burden (TMB) = 3.1, microsatellite stability (MSS) ( Figure 4A ,  Supplementary Figure S1 ). Immunohistochemistry (IHC): EBV (-), PD-L1 CPS = 3, HER-2 (3+) ( Figures 4B-D ).