Successful Alectinib Treatment for Carcinoma of Unknown Primary with EML4-ALK Fusion Gene: A Case Report

Gene alteration in anaplastic lymphoma kinase (ALK) is rare, and the efficacy of ALK inhibitors in the treatment of carcinoma of unknown primary (CUP) with ALK alteration remains unclear. The patient was a 56-year-old woman who presented with cervical lymph node swelling. Computed tomography revealed paraaortic, perigastric, and cervical lymph node swelling; ascites; a liver lesion; and a left adrenal mass. A cervical lymph node biopsy was performed, and pathological diagnosis of an undifferentiated malignant tumor was conducted. Finally, the patient was diagnosed with CUP and treated with chemotherapy. To evaluate actionable mutations, we performed a multigene analysis, using a next-generation sequencer (FoundationOne® CDx). It revealed that the tumor harbored an echinoderm microtubule-associated protein-like 4 (EML4) and ALK fusion gene. Additionally, immunohistochemistry confirmed ALK protein expression. Alectinib, a potent ALK inhibitor, was recommended for the patient at a molecular oncology conference at our institution. Accordingly, alectinib (600 mg/day) was administered, and the multiple lesions and symptoms rapidly diminished without apparent toxicity. The administration of alectinib continued for a period of 10 months without disease progression. Thus, ALK-tyrosine kinase inhibitors should be considered in patients with CUP harboring the EML4-ALK fusion gene. READ ARTICLE

Current Oncology DOI: 10.3390/curroncol28030180

Authors: Sugiyama K., Izumika A., Iwakoshi A., Nishibori R., Sato M., Shiraishi K., Hattori H., Nishimura R. and Kitagawa C.

Circulating tumor cells as a response biomarker in alk-positive metastatic inflammatory myofibroblastic tumor

Case report of a 19-year-old boy with an ALK-positive IMT of the bladder, proximal osteolytic and multiple bilateral lung lesions, who received ALK inhibitor entrectinib postoperatively and underwent longitudinal CTC analysis during treatment. Antitumor activity of entrectinib was demonstrated and was accompanied by regression of lung lesions, elimination of CTCs from the blood and no development of relapses afterwards. Therapy continued without any clinical sign of progression and 24 months since the initiation of treatment the patient remains symptom-free and disease-free. READ ARTICLE

Frontiers in Pediatrics DOI:10.3389/fped.2021.652583

Authors: Paolo Bonvini, Elisabetta Rossi, Angelica Zin, Mariangela Manicone, Riccardo Vidotto, Antonella Facchinetti, Lucia Tombolan, Maria C. Affinita, Luisa Santoro, Zamarchi Rita, Gianni Bisogno.

Complex genetic alterations contribute to rapid disease progression in an ALK rearrangement lung adenocarcinoma patient: a case report

Concurrent genetic alterations, including loss-of-function mutations in FBXW7 and MLL3, may mainly contribute to poor prognosis in the patient. It highlighted the molecular profiling by using NGS can be useful in identifying the heterogeneity across lesions and the resistance mechanism of targeted treatments. READ ARTICLE

Translational Cancer Research DOI:10.21037/tcr-20-3473

Authors: Xiang Long, Hao Wu, Chenglin Yang, Fang Li, Min Zhang, Xuan Wu

Crizotinib in Patients With MET-Amplified NSCLC

Patients with high-level, MET-amplified NSCLC responded to crizotinib with the highest ORR. Use of combined diagnostics for MET and other oncogenes may potentially identify patients most likely to respond to crizotinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.02.010

Authors: D. Ross Camidge, Gregory A. Otterson, Jeffrey W. Clark, Sai-Hong Ignatius Ou, Jared Weiss, Steven Ades, Geoffrey I. Shapiro, Mark A. Socinski, Danielle A. Murphy, Umberto Conte, Yiyun Tang, Sherry C. Wang, Keith D. Wilner, Liza C. Villaruz

Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib

The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy. READ ARTICLE

Translational Lung Cancer Research DOI:10.21037/tlcr-21-160

Authors: Jingjing Li, Bin Zhang, Yu Zhang, Feng Xu, Zhenfa Zhang, Lin Shao, Chunhe Yan, Paola Ulivi, Marc G Denis, Petros Christopoulos, Vincent Thomas de Montpréville, Eric H Bernicker, Anthonie J van der Wekken, Changli Wang, Dongsheng Yue

Immunotherapy Treatment Patterns and Outcomes Among ALK-Positive Patients With Non–Small-Cell Lung Cancer

Real-world effectiveness (rwPFS) of ICIs in ALK-positive NSCLC patients, whether provided before or after TKIs, was limited, underscoring the relative lack of efficacy of ICI in this patient population, particularly compared to approved ALK TKIs. READ ARTICLE

Clinical Lung Cancer DOI: 10.1016/j.cllc.2020.08.003

Authors: Mohammad Jahanzeb, Huamao M.Lin, Xiaoyun Pan, Yu Yin, Pia Baumann, Corey J. Langer

The role of plasma genotyping in ALK- and ROS1-rearranged lung cancer

Review discusses technical aspects of plasma genotyping strategies and summarize findings from studies exploring plasma genotyping (including ctDNA analysis and profiling of nucleic acids contained in other plasma components) in two rearrangement-driven NSCLC subsets (ALK-rearranged and ROS1-rearranged). READ ARTICLE

Translational Lung Cancer Research DOI: 10.21037/tlcr-2019-cnsclc-09

Authors: Dagogo-Jack I, Ritterhouse LL.

Review PaperKirk SmithDecember 9, 2020ctDNA, next-generation sequencing, NGS, ALK, liquid biopsy

Anaplastic lymphoma kinase (ALK) partners identified by next-generation sequencing in Chinese patients with solid tumors

Background: Anaplastic lymphoma kinase (ALK) rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC). More than 30 different fusion partner genes of ALK in NSCLC have been reportedand most of these ALK fusions respond well to ALK inhibitors crizotinib. With the development of next-generation sequencing (NGS), more novel partners for ALK rearrangement have been identified. Here, we aimed to report the landscape of ALK rearrangement in Chinese patients with solid tumors... Conclusions: Novel ALK fusions are detected in patients with not only NSCLC but also other solid tumors. NGS fusion assay is an optional method for screening novel fusions. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.3555

Authors: Sheng Yang, Fuyu Gong, Guoqiang Wang, Xiaohui He

Responses to ALK Inhibitor Treatments in a Patient with Non-Small Cell Lung Cancer Harboring a Novel HPCAL1-ALK Fusion Variant: A Case Report

Anaplastic lymphoma kinase (ALK) fusion is present in approximately 2–7% of patients with lung adenocarcinoma. ALK fusion-positive patients can benefit from targeted therapy. We herein report a 53-year-old Chinese male patient diagnosed as lung adenocarcinoma with a smoking history. Next-generation sequencing was performed to detect somatic mutations of oncogenic drivers and tumor suppressor genes in plasma-derived circulating tumor DNA using an ultra-deep 160-gene panel. A novel HPCAL1-ALK fusion variant was identified in the patient responding to ALK inhibitor treatments, and the fusion variant was also confirmed by fluorescence in situ hybridization and immunohistochemical. Our study expands the mutational spectrum of ALK fusion variants and provides options for the precise treatment of such patients. READ ARTICLE

OncoTargets and therapy DOI:10.2147/OTT.S252210

Authors: Wang R, Qin J, Fan Y, Li Z, Chen C, Su W.