PMC9207953_01
Representative magnetic resonance imaging (MRI) images of lesions. (A-D) Representative images of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) in the liver. (E-I) Representative images of rectum lesions in the sagittal position and coronal position (T1WI, T2WI, DWI and ADC), respectively. Red arrows indicate typical liver or rectum lesions.
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Subsequently, the patient was diagnosed with middle rectum adenocarcinoma with liver metastasis after conducting a pathological biopsy and magnetic resonance imaging (MRI) of the liver and rectum ( Figure 1 ), accompanied with elevated CA199 (>1000.00 U/ml) and CEA (229.70 ng/ml), suggesting a stage of cT3NxM1a, stage IVA according to National Comprehensive Cancer Network (NCCN) staging criteria.
Representative computed tomography (CT) images of liver lesions during treatment. (A) Before first-line treatment, the representative CT image of the liver. (B) Regular CT was used to assess treatment efficacy during first-line treatment containing FOLFIRI plus cetuximab. (C) Regular revision CT was used to assess treatment efficacy during second-line treatment containing XELOX plus bevacizumab. (D) CT image of liver lesions after two cycles of regorafenib. (E) CT images of liver lesions after two cycles and four cycles of rechallenging FOLFIRI plus cetuximab. Red arrows indicate typical liver lesions. CT computed tomography; FOLFIRI, chemotherapy regimen containing irinotecan and fluorouracil; XELOX, chemotherapy regimen containing capecitabine and oxaliplatin.
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After two cycles of therapy, his tumor shrank remarkably, and partial response (PR) was assessed ( Figures 2A, B ), followed by stable disease (SD) based on Response Evaluation Criteria in Solid Tumors (RECIST); simultaneously accompanying with reduced CA199 (30.73 U/ml) and CEA values (21.18 ng/ml) in blood after four cycles. However, disease progressed in November 2018, mainly referring to the liver metastasis ( Figure 2B ). During six cycles, his metastasis lesion size in the liver remained stable, and even shrunk ( Figure 2C ), with the copy number of KRAS decreasing to 2.69 copies and mutant frequency of Table 1 ). After finishing the second-line therapy, abdominal enhanced CT scanning showed that the size of the liver lesion had enlarged ( Figure 2C ). The patient was subsequently treated with third-line regorafenib. Unfortunately, it failed to control the tumor growth ( Figure 2D ). And tumor markers of CA199 and CEA decreased gradually. Although his liver lesions enlarged and the number of lesions also increased after six cycles, the physician considered that it might be due to the prolonged treatment interval ( Figure 2E ).
Changes in KRAS copy number, CA199, and CEA level during anti-tumor treatment and follow-up of the patient. The KRAS copy number was measured in the patient's circulating tumor DNA. The CA199 and CEA tumor markers were measured in the patient's serum at periodic intervals throughout the clinical course and annotated with the date, therapeutic approach, and treatment efficacy. CA199, cancer antigen 199; CEA, carcinoembryonic antigen; SD, stable response; PR, partial response; FOLFIRI, chemotherapy regimen containing irinotecan and fluorouracil; XELOX, chemotherapy regimen containing capecitabine and oxaliplatin.
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The patient decided to stop the treatment and never returned to the hospital after the last outpatient follow-up in March 2020.  Figure 3  presents the whole process and dynamics in tumor-related markers.