PMC9366196_01
Treatment history and clinical information of the presented case. (A) The medical history of the presented case is shown with information about treatment timeline, response evaluation, and sample collection timepoints. During the combination treatment with everolimus and apatinib, plasma ctDNA sequencing was performed every 3 months along with treatment response evaluation as indicated by the arrowheads. (B) H&E staining and immunohistochemical (IHC) examinations (x200) of the primary uterine PEComa which was negative for the SMA marker and positive for Melan-A (90%). The Ki67 index is 20%. (C) CT images of lung metastases during everolimus and apatinib treatment. Lesions are indicated by the red arrows. PR, partial response; SD, stable disease; PD, progressive disease; NGS, next-generation sequencing; PEComa, perivascular epithelioid cell tumors; ctDNA, circulating tumor DNA; FFPE, formalin-fixed, paraffin-embedded; H&E, hematoxylin and eosin; SMA, smooth muscle actin.
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The color Doppler ultrasound revealed a mass in the right side of the uterus, which was surgically removed ( Figure 1AM ). Ki67 labeling in the tumor cells was 20% ( Figure 1B ). In March 2018, the patient received intraperitoneal chemotherapy with cisplatin (80 mg) and sodium bicarbonate (150 ml), but the disease progressed rapidly with the development of lung and bone metastases within 2 months ( Figure 1C ).
Changes in NSE and CA125 levels, and the allele frequencies (AFs) of TP53 and TSC2 mutations during apatinib and everolimus treatment. The levels of the lung cancer biomarkers NSE (neuron-specific enolase) and CA125 (cancer antigen 125) in serum examined every 3 months are shown by the green and orange lines, respectively. Plasma ctDNA sequencing was also performed every 3 months during apatinib and everolimus treatment. The AFs of TP53 R273P (blue) and TSC2 P1497H (light blue) mutations are shown by the dark blue and light blue lines, respectively. The units of NSE, CA125, and AF were indicated by the different y-axes.
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The levels of neuron-specific enolase (NSE) and cancer antigen 125 (CA125) were 38.52 and 21.2 U/ml, respectively ( Figure 2 ). The patient achieved a partial response (PR) after 3 and 6 months of apatinib and everolimus treatment, after which the plasma ctDNA was still tested negative for genomic alterations and the levels of NSE and CA125 were dramatically decreased ( Figure 2 ). Additionally, the levels of NSE and CA125 were slightly but continuously increased after 9 and 12 months of combined treatment ( Figure 2 ).