PMC8554320_01
Timeline of the clinical course in this patient.
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Chest computed tomography (CT) revealed a large, soft tissue mass of 12.43 x 10.22 cm in the right middle lobe and a massive right pleural effusion (Figure 1). Abdominal CT showed liver hypodensity with a nodule measuring 2.83 x 2.76 cm (Figure 1). Local hypodensity shadow of the kidney was present on both sides, with a mass of 4.53 x 4.26 cm in the left kidney and 4.16 x 3.36 cm in the right kidney (Figure 1). ALK expression (Figure 3C). Alectinib (600 mg BID) combined with irinotecan (CPT-11; 0.4g dl) as second-line therapy was administered. After two cycles of treatment, CT scan showed a partial response (PR) with a reduction from 15.0 x 12.6 cm to 8.42 x 5.16 cm for lung lesion (Figure 1). During the 4th, 6th and 8th cycles after treatment, the tumor lesions continued to decrease, and the patient maintained PR (Figures 1 and 4).
Multi-biomarker immunohistochemistry confirms pathological typing of small cell lung cancer. (A) HE, (B) CD56, (C) Syn, (D) CgA, (E) Ki-67, (F) TTF-1, (G) p40, (H) CEA and NSE, (I) CA19-9.
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IV, Figure 2A) with immunoreactivity to CD56, Synaptophysin (Syn), CgA and Ki-67 (about 90% positive), and negative for TTF-1 and p40 on (Figure 2B-G). In addition, laboratory examinations revealed elevations in the levels of neuron-specific enolase (NSE; 179 ng/mL), whereas no abnormalities were observed in carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). Meanwhile, the levels of NSE ( 300 ng/mL), CA19-9 (24.8 U/mL) and CEA (2.13 ng/mL) were increased (Figure 2H and I).
Next-generation sequencing results. (A) Next-generation sequencing analysis of ALK fusion mutation in the patient's biopsy sample. (B) The MAF of mutated genes. (C) Immunohistochemical staining of ALK expression.
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To seek potential therapeutic regimens, the blood specimen was subjected to NGS analysis, and a novel ALK and intergenic region (IR) rearrangement was identified (mutant allele frequency [MAF]: 19.21%, Figure 3A and B). ALK expression (Figure 3C). Alectinib (600 mg BID) combined with irinotecan (CPT-11; 0.4g dl) as second-line therapy was administered. After two cycles of treatment, CT scan showed a partial response (PR) with a reduction from 15.0 x 12.6 cm to 8.42 x 5.16 cm for lung lesion (Figure 1). NGS-based ctDNA test showed a decrease in MAF of ALK rearrangement (from 19.21% to 0.58%, Figure 3B). In addition, ALK rearrangement had disappeared after 4 cycles of treatment (Figure 3B).
Computed tomography scan of metastatic lesions after treatment.
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Meanwhile, the size of liver tumor (2.0 x 1.57 cm) and bilateral kidney tumor (left: 3.3 x 2.37 cm; right: 3.05 x 2.18 cm) were decreased (Figure 4). During the 4th, 6th and 8th cycles after treatment, the tumor lesions continued to decrease, and the patient maintained PR (Figures 1 and 4).