Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report.

More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.

Lobe-specific analysis of perioperative chemotherapy for non-small cell lung cancer patients.

OBJECTIVES: Perioperative cisplatin-based chemotherapy decreases the risk of death over surgery alone and is a standard of care. Here, we examined perioperative chemotherapy indications for stage IB-III non-small cell lung cancer (NSCLC) patients according to lobe-specific analysis. METHODS: Resectable NSCLC patients with stage IB-III who received perioperative chemotherapy with and without radiotherapy after lung resection were identified from the SEER database. Propensity score matching (PSM) analysis was performed to reduce the inherent bias of retrospective studies. The Kaplan-Meier method and log-rank tests were used to assess the differences in overall survival (OS). RESULTS: The study enrolled 23,844 patients before PSM. The perioperative chemotherapy group had better OS than the nonperioperative chemotherapy group in stage IB-III NSCLC patients before and after PSM. However, subgroup analysis according to stage demonstrated that perioperative chemotherapy did not markedly benefit patients with stage IB. Furthermore, lobar subgroup analysis did not show survival advantages in primary tumors located in either the right middle lobe in stages II and III NSCLC or the right lower lobe in stage III NSCLC. CONCLUSIONS: Lobe-specific perioperative chemotherapy is recommended in NSCLC patients. For stage IB NSCLC, right middle lobe NSCLC from stage IB-III and right lower lobe NSCLC from stage III, perioperative chemotherapy might not confer survival benefits.

Necroptosis-related lncRNA in lung adenocarcinoma: A comprehensive analysis based on a prognosis model and a competing endogenous RNA network.

Background: Necroptosis, an innovative type of programmed cell death, involves the formation of necrosomes and eventually mediates necrosis. Multiple lines of evidence suggest that necroptosis plays a major role in the development of human cancer. However, the role of necroptosis in lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to construct an NRL-related prognostic model and comprehensively analyze the role of NRL in LUAD. Methods: A necroptosis-related lncRNA (NRL) signature was constructed in the training cohort and verified in the validation and all cohorts based on The Cancer Genome Atlas database. In addition, a nomogram was developed. The tumor microenvironment (TME), checkpoint, human leukocyte antigen, and m6A methylation levels were compared between low-risk and high-risk groups. Then, we identified five truly prognostic lncRNAs (AC107021.2, AC027117.1, FAM30A, FAM83A-AS1, and MED4-AS1) and constructed a ceRNA network, and four hub genes of downstream genes were identified and analyzed using immune, pan-cancer, and survival analyses. Results: The NRL signature could accurately predict the prognosis of patients with LUAD, and patients with low risk scores were identified with an obvious "hot" immune infiltration level, which was strongly associated with better prognosis. Based on the ceRNA network, we postulated that NRLs regulated the TME of patients with LUAD via cyclin-dependent kinase (CDK) family proteins. Conclusion: We constructed an NRL signature and a ceRNA network in LUAD and found that NRLs may modulate the immune microenvironment of LUAD via CDK family proteins.