PMC8417525_01
Representative clinical images obtained during the course of treatment. (A) FDG-PET/CT of the brain, lung, and mediastinum before (2020/02) and after (2021/04) TKI therapy. (B) Hematoxylin and eosin (HE) staining of the tumor biopsy revealed a few atypical glands. Immunohistochemical staining of thyroid transcription factor (TTF1) (C), p40 (D), and Ki-67 (E) of the tumor biopsy (400x).
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Chest computed tomography (CT) and positron emission tomography (PET)-CT scanning revealed multiple tumor lesions in the inferior lobe of the right lung and the occipital lobe of the brain, which was clinically suggestive of lung cancer and brain metastases (BMs) (Figure 1A). Histological analysis of the tumor biopsy showed a few atypical glands (Figure 1B), and immunohistochemistry staining (IHC) of the tumor biopsy revealed remarkable positivity for thyroid transcription factor (TTF1) and Ki-67 (50%) (Figures 1C, E) and negativity for p40 (Figure 1D). The PET-CT scan in April 2021 revealed decreased tumor lesions in her right lung and brain which indicated an SD (Figure 1A).
Sequence analysis of the STK3-ALK fusion. (A) DNA and (B) RNA-level fusion reads of STK3-ALK are shown from the Integrative Genomics Viewer. (C) A schematic map showing the structure of the STK3-ALK fusion locus. Exons 1-6 of STK3 (purple) were fused to exons 20-29 of ALK (green) through intron6 of STK3 and intron19 of ALK. (D) Immunohistochemical staining revealed the diffuse expression of ALK in tumor cells (20x).
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Interestingly, a novel STK3-ALK rearrangement was identified with a mutant allele frequency of 3.1% (Figure 2A). RNA sequencing (RNA-seq) confirmed the novel fusion (Figure 2B), and anti-ALK immunohistochemistry revealed a high level of ALK protein expression (Figure 2D).
Radiological features before and after crizotinib therapy. (A) Timeline of therapies for advanced NSCLC. (B) The chest CT and brain MRI scans reveal the control of disease after crizotinib treatment. Tumors are indicated by red arrows. CT, computed tomography; MRI, magnetic resonance imaging; SRS, stereotactic radiosurgery; MAF, mutant allele frequency; SD, stable disease; PD, progressive disease.
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Therefore, crizotinib (250 mg, bid) plus stereotactic radiosurgery (SRS, 28Gy/3fx/5fx) to the brain was recommended as the first-line treatment beginning in March 2020 (Figure 3A). Unfortunately, after 8 months of crizotinib therapy, an MRI scan revealed progressive disease (PD), manifesting as central nervous system (CNS) progression (Figure 3B).