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Medicine (Baltimore)
2022 Aug 26;10134:e30255. doi: 10.1097/MD.0000000000030255.
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Excellent response of lung adenocarcinoma harboring a rare SLC8A1 downstream intergenic region ALK fusion to ceritinib treatment: A case report.
Fang L
,
Ding G
,
Wang M
,
Ye Y
,
Yan X
,
Ding P
,
Wang J
,
Zhang Y
.
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RATIONALE: Anaplastic lymphoma kinase (ALK) gene fusion, an important driver gene alteration leading to the development of lung cancer, occurs in 5% of nonsmall cell lung cancer (NSCLC) cases in China. In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK, which is the most common type of ALK fusion, various fusion partner genes have been identified in recent years. However, ALK intergenic breakpoint fusions confound fusion detection and targeted treatment.
PATIENT CONCERNS: A 40-year-old woman presented to our hospital with a 2-month history of a cough.
DIAGNOSIS: Based on the right hilar lymph node biopsy and positron emission tomography computed tomography (PET-CT) examination, the patient was diagnosed with "stage IV lung adenocarcinoma" showing metastases in the mediastina, right hilar lymph nodes, and C7 vertebral body. A rare solute carrier family 8 member A1 (SLC8A1) downstream intergenic region ALK fusion was identified in biopsy specimens using next-generation sequencing (NGS).
INTERVENTIONS: The patient received first-line molecular-targeted therapy (ceritinib).
OUTCOMES: After nearly 9 months, the best evaluation of partial remission (PR) was obtained.
LESSONS: This is the first clinical evidence of advanced NSCLC due to a rare SLC8A1 downstream intergenic region ALK fusion that has been effectively treated with ceritinib. Whether this finding represents an inherent property of this fusion protein or its unique clinicopathological characteristics in patients carrying this fusion protein remains to be investigated. Moreover, the patient's durable response to ceritinib and future resistance mechanisms require further follow-up.
Figure 1. A Chinese female patient was diagnosed with stage IV lung adenocarcinoma. (A) Positron emission tomography computed tomography (PET-CT) indicated localized malignant lesions in the lower lobe of the right lung and mediastinal and right hilar lymph nodes. (B) Immunohistochemical (IHC) analysis showed that the tumor cells were positive for TTF-1, NapsinA and CK7 and negative for P40, P63, and Syn (×200).
Figure 2. A rare SLC8A1 downstream intergenic region ALK fusion was discovered in the patient’s biopsy specimen. (A) Integrative Genomics Viewer (IGV) showed the SLC8A1-ALK intergenic fusion detected by capture-based next-generation sequencing (NGS) from right hilar lymph node metastasis formalin-fixed, paraffin-embedded clinical sample. (B) A diagram of the SLC8A1-ALK intergenic fusion. (C) Confirmation of the ALK fusion by real-time quantitative polymerase chain reaction (qPCR). (D) Immunohistochemistry (IHC) staining indicated a strong expression of ALK (D5F3 antibody).
Figure 3. Dynamic monitoring of the response of the patient with lung adenocarcinoma to ceritinib. (A) Chest computed tomography (CT) scans on September 11, 2020 revealed the presence of a mass in the lower lobe of the right lung and enlargement of mediastinal and right hilar lymph nodes. Significant (December 18, 2020) (B) and consistent (February 24, May 3 and July 9, 2021) (C–E) reduction of the tumor volume and enlargement of mediastinal/right hilar lymph nodes were observed by the follow-up CT scans after the first-line therapy with ceritinib. (F) Positron emission tomography computed tomography (PET-CT) scanning on September 17, 2020 revealed bone metastasis at the C7 vertebral body. (G) Emission computed tomographic (ECT) bone scanning after treatment with ceritinib for 6 months showed bone metastasis disappeared. (H) Dynamic change of serum carcinoembryonic antigen (CEA) level and intergenic region ALK mutation frequency in peripheral blood ctDNA during the treatment course.
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