PMC10366596_01
Abdominal CT images and gastroscopic images of the two independent lesions during the course of the treatment. Gastroscopic images of the two independent lesions from cardia (L-O) and fundus (H-K) are shown as well as the HE stain (P-R). Lesions in abdominal CT images (A-G) during treatment are indicated by the red arrows.
fonc-13-1195837-g001.jpg
PMC10366596_01_fonc-13-1195837-g001.jpg
f1
Figure 1A ), along with the presence of multiple lymph nodes in the hepatogastric ligament region and posterior pancreatic nodules suggestive of tumor metastasis. Further, Positron Emission Tomography-Computed Tomography (PET-CT) indicated malignancies in the gastric cardia and the inferior and posterior gastric walls, accompanied by multiple lymph node metastases. Gastroscopy revealed multiple ulcerative lesions throughout the stomach, with irregular elevation of the surrounding mucosa ( Figures 1H, L ). Gastroscopic biopsy and immunohistochemical (IHC) staining of the cardia confirmed the presence of adenocarcinoma ( Figure 1P ), with strong positive expression of HER-2 (HER-2+++). By November, the disease achieved partial response (PR) according to imaging assessments ( Figure 1B ). Figure 1C ). Following six cycles of chemotherapy, the patient was transitioned to long-term maintenance with oral Tegio capsules and scheduled for regular followed-up visits at the clinic. In July 2020, the patient was admitted to the hospital due to abdominal pain and emaciation, and was confirmed to have progressive disease (PD) by a CT scan ( Figure 1D ). Gastroscopy revealed two lesions in the cardia and antrum, with normal mucosa observed between the two regions ( Figures 1I, M ). Interestingly, while both lesions were diagnosed as adenocarcinoma ( Figure 1Q ), IHC staining showed HER2 positivity only in the cardia, and not in the antrum. NGS profiling at three months after initiating treatment demonstrated a substantial decrease in circulating tumor DNA (ctDNA) levels ( Figure 3 ), which was consistent with stable disease (SD) of the lesions ( Figure 1E ). At five months following chemo-immune combination therapy, the antrum lesion achieved complete response (CR), the cardia and body lesions achieved partial response (PR) as evaluated by CT scans and Gastroscopy ( Figures 1F, J, N ). CCNE1 amplifications were detected at copy numbers of 3.5 and 3.6, respectively. Subsequently, trastuzumab was re-introduced to the treatment regimen in February 2021. The therapy was continued for five months until July 2021, when the patient presented with a new gastric body mass ( Figures 1G, K, O, R ), and ctDNA was detected in the plasma ( Figure 2 ). Compared to the previously analyzed lesions, the mutational profile of the newly developed body mass was highly consistent with that of the cardia lesion, suggesting metastasis.
Diagnosis and treatment process of the presented case. The medical history of this SMGC case is shown with genetic information, treatment schedule, timeline and response evaluation. Plasma ctDNA sequencing was performed along with treatment response evaluation as indicated during the sequential treatment.
fonc-13-1195837-g002.jpg
PMC10366596_01_fonc-13-1195837-g002.jpg
f2
IIIc) ( Figure 2 ). In September, due to the lack of motivation and personal preference, the patient was treated with first-line chemotherapy, consisting of oxaliplatin (Eloxatin) injection at a dose of 200 mg on Day 1, and Tegio capsules at a dose of 40 mg orally, twice daily from Day 1 to Day 14, with treatment cycles repeated every three weeks for a maximum of three cycles. CCNE1 amplifications were detected at copy numbers of 3.5 and 3.6, respectively. Subsequently, trastuzumab was re-introduced to the treatment regimen in February 2021. The therapy was continued for five months until July 2021, when the patient presented with a new gastric body mass ( Figures 1G, K, O, R ), and ctDNA was detected in the plasma ( Figure 2 ). Compared to the previously analyzed lesions, the mutational profile of the newly developed body mass was highly consistent with that of the cardia lesion, suggesting metastasis.
Changes in the allele frequencies (AFs) of mutations detected in serial plasma ctDNA during treatment. The X-axis represents the time points of plasma ctDNA sequencing, and the Y-axis indicates the AFs of different mutations, represented by color-coded lines. As shown in the figure, the AF levels of nearly all mutations exhibited varying degrees of decline following treatment.
fonc-13-1195837-g003.jpg
PMC10366596_01_fonc-13-1195837-g003.jpg
f3
NGS profiling at three months after initiating treatment demonstrated a substantial decrease in circulating tumor DNA (ctDNA) levels ( Figure 3 ), which was consistent with stable disease (SD) of the lesions ( Figure 1E ).