PMC9871888_01
Representative axial computed tomography images. (A) Image depicting the disease status before liquid biopsy, with an ill-defined heterogeneous mass about 5.4 cm at the pancreatic head (dotted arrows) and multiple liver metastases 9arrow) (B) Subsequent imaging following 3 months of entrectinib treatment (600 mg/day) illustration the resolution of the pancreatic tumor (sized 4.2 cm) and liver metastases (C) After 6 months of entrectinib with a further resolution of the tumors. The pancreatic tumor sized only 3.8 cm (D) Disease progression (pancreatic tumor sized 7.4 cm) and increased number of liver metastases.
fonc-12-1031396-g001.jpg
PMC9871888_01_fonc-12-1031396-g001.jpg
f1
Follow-up computed tomography (CT) in August 2020 indicated disease progression with the pancreatic tumor sized 5.4 cm and the largest hepatic metastatic tumor sized 4.2 cm, and lymphadenopathies ( Figure 1A ). Three months later, CT revealed shrinkage of the pancreatic and liver tumors with the pancreatic tumor sized 4.2 cm and the largest hepatic lesion of 3 cm ( Figure 1B ). In January 2021, a follow-up CT indicated further resolution of the pancreatic and liver lesions, sized 3.8 cm and 2.4 cm, respectively ( Figure 1C ). CT revealed a markedly increased number of liver tumors and the enlarged diameter of pancreatic tumor of 7.4 cm ( Figure 1D ). Concurrently, the patient's total bilirubin increased from 0.87 to 8.18 mg/dL.
Serial cell-free DNA analysis. Circulating tumor DNA was assessed before entrectinib treatment and at treatment failure. After 8 months of entrectinib, the variation allele frequency of ETV6-NTRK3 decreased, and the RAS mutation became undetectable. However, NTRK3-G623R and NTRK3-G623E mutations emerged.
fonc-12-1031396-g002.jpg
PMC9871888_01_fonc-12-1031396-g002.jpg
f2
The cfDNA analysis demonstrated the emergence of NTRK3-G623R and NTRK-G623E mutations, and the RAS mutation was undetectable ( Figure 2 ).
Scheme of clinical course with gene mutation tests.
fonc-12-1031396-g003.jpg
PMC9871888_01_fonc-12-1031396-g003.jpg
f3
TRK inhibitor targeting acquired NTRK fusion mutations. The clinical course with genomic change identified was illustrated in  Figure 3 .