case_images: PMC11783296_01
case_images: Schematic of common gene alterations across the treatment timeline in case 1 patient.
case_images: oyae020_fig1.jpg
case_images: PMC11783296_01_oyae020_fig1.jpg
case_images: F1
case_images: ALK gene with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) resulting from an inversion within chromosome 2 and the fusion of exons 1-35 of CAD with exons 20-29 of ALK (Fig. 1). According to previously published reports, CAD-ALK gene rearrangements in patients with CRC can be treated using ALK-TKIs. An ALK p.G1202R resistant mutation was detected, as well as a lower allele frequency of CAD-ALK fusion (0.9%), ALK-CAD fusion (1.0%), and CDKN2A mutation (0.8%) (Fig. 1). The NGS result showed that the ALK p.G1202R mutation and the other genetic alterations had all disappeared (Fig. 1).
case_images: Computed tomography imaging of metastatic lesions before and after ALK-TKIs treatment in case 1 patient (A). The serum levels of CEA and CA 19-9 before and after ALK-TKIs treatment in case 1 patient (B).
case_images: oyae020_fig2.jpg
case_images: PMC11783296_01_oyae020_fig2.jpg
case_images: F2
case_images: After 1 month of this treatment, another CT scan revealed a partial response (PR) for retroperitoneal lymphadenectasis (Fig. 2A) and a concomitant decrease in serum CEA and CA 19-9 levels (Fig. 2B). After receiving fruquintinib combined with ensartinib for 4 months, the patient was assessed for progressive disease (PD) with multiple retroperitoneal lymph node metastases accompanied by elevated serum CEA and CA 19-9 (Fig. 2B). ALK-TKI was recommended at a dose of 100 mg qd, beginning on May 11, 2023. Another CT scan revealed shrinkage of the retroperitoneal and hilar hepatic metastatic nodules (Fig. 2A).
case_images: PMC11783296_02
case_images: Schematic of common gene alterations in case 2 patient.
case_images: oyae020_fig3.jpg
case_images: PMC11783296_02_oyae020_fig3.jpg
case_images: F3
case_images: Genetic testing suggested wild-type KRAS/NRAS/BRAF, EML4-ALK fusion, and TP53 mutations in p.R273C (Fig. 3).
case_images: Computed tomography imaging of metastatic lesions before and after alectinib treatment in case 2 patient.
case_images: oyae020_fig4.jpg
case_images: PMC11783296_02_oyae020_fig4.jpg
case_images: F4
case_images: The recurrence of multiple metastases to the lungs, mediastinum, and retroperitoneal lymph nodes was detected in April 2022 (Fig. 4). A repeat CT revealed continuous shrinkage of the pulmonary metastatic nodules, mediastinal metastatic lymph nodes, and retroperitoneal lymphadenectasis (Fig. 4).