scholarly journals Successful Treatment of a Resistant Subclone in ALK-Rearranged NSCLC

2020 ◽  
Vol 13 (2) ◽  
pp. 729-732
Author(s):  
David König ◽  
Urs R. Meier ◽  
Bernd Klaeser ◽  
Spasenija Savic ◽  
Miklos Pless
Keyword(s):  
Liquid Biopsy ◽  
Progressive Disease ◽  
Kinase Inhibitors ◽  
Treatment Approach ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Pet Ct Scan ◽  
Resistant Mutation

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are established effective therapies in patients with ALK-rearranged advanced non-small-cell lung cancer (NSCLC). Upon progressive disease, patients normally receive a subsequent ALK TKI. However, when disease progression occurs in a limited number of sites, an oligoprogressive approach is a treatment option. In our case, FDG-PET/CT scan detected a progressive site in a patient with ceritinib therapy. Biopsy of the lesion was not possible because of its location. Progression was therefore confirmed by liquid biopsy with identification of the resistant subclone ALK G1202R. Definitive radiotherapy of the progressive site led to the disappearance of the ALK-resistant mutation. Meanwhile, ceritinib therapy was continued. The absence of disease both on repeated imaging and liquid biopsy indicates that eradication of a resistant subclone with an oligoprogressive treatment approach might be possible.

scholarly journals Liquid biopsy for monitoring anaplastic lymphoma kinase inhibitors in non-small cell lung cancer: two cases compared

2017 ◽  
Vol 9 (S13) ◽  
pp. S1391-S1396 ◽  
Author(s):  
Mariangela Manicone ◽  
Maria Chiara Scaini ◽  
Maria Grazia Rodriquenz ◽  
Antonella Facchinetti ◽  
Alfredo Tartarone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Liquid Biopsy ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Dual-time point 18F-FDG PET/CT scan for differentiation between 18F-FDG-avid non-small cell lung cancer and benign lesions

2009 ◽  
Vol 23 (5) ◽  
pp. 427-435 ◽  
Author(s):  
Kazuyoshi Suga ◽  
Yasuhiko Kawakami ◽  
Atsuto Hiyama ◽  
Kazurou Sugi ◽  
Kazutomo Okabe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Fdg Pet ◽  
Small Cell ◽  
Benign Lesions ◽  
Small Cell Lung ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Pet Ct Scan ◽  
Time Point

scholarly journals THU0319 DEVELOPMENT AND OUTCOME OF AORTIC COMPLICATIONS DURING TOCILIZUMAB TREATMENT OF GCA AND HISTOPATHOLOGIC EVIDENCE OF RESIDUAL INFLAMMATION-A CASE SERIES.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 388.2-389
Author(s):  
A. Rubbert-Roth ◽  
P. K. Bode ◽  
T. Langenegger ◽  
C. Pfofe ◽  
T. Neumann ◽  
...  
Keyword(s):  
Structural Changes ◽  
Case Series ◽  
Aortic Aneurysms ◽  
Imaging Data ◽  
Limited Data ◽  
Retrospective Case ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Pet Ct Scan

Background:Giant cell arteritis (GCA) may affect the aorta and the large aortic branches and lead to dissections and aortic aneurysms. Tocilizumab (TCZ) treatment has the capacity to control aortic inflammation as has been demonstrated by CRP normalization and imaging data. However, limited data are available on the histopathological findings obtained from patients who underwent surgery because of aortic complications during TCZ treatment.Objectives:We report on 5 patients with aortitis who were treated with TCZ and developed aortic complications.Methods:We describe a retrospective case series of patients with GCA treated with TCZ, who presented in our clinic between 2011 and 2019. Three patients underwent surgery. Histopathologic examination was performed in specimen from all of them.Results:Five female patients were diagnosed with GCA (4/5) or Takaysu arteritis (1/5) involving the aorta, all them diagnosed by MR angiography and/or FDG PET CT scan. Three patients (one with aortic aneurysm, one with dissection) underwent surgery after having been treated with TCZ for seven weeks, nine months and four years, respectively. Imaging before surgery showed remission on MRI and/or PET-CT in all cases. At the time of surgery, all patients showed normalized CRP and ESR values. Histopathological evaluation of the aortic wall revealed infiltrates, consisting predominantly of CD3+CD4+ T cells. Enlargement of pre-existing aneuryms was observed in the other two patients 10 weeks and 4 months after discontinuation of TCZ, respectively. Both patients were not eligible for surgical intervention and died during follow-up.Conclusion:Our case series suggests that during treatment with TCZ, regular imaging is necessary in this patient population to detect development of structural changes such as aneurysms or dissections. Despite treatment, residual inflammation might persist which could contribute to eventual aortic complications.Disclosure of Interests:Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Peter Karl Bode: None declared, Thomas Langenegger: None declared, Claudia Pfofe: None declared, Thomas Neumann: None declared, Olaf Chan-Hi Kim: None declared, Johannes von Kempis Consultant of: Roche

scholarly journals Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marianne Oulhen ◽  
Patrycja Pawlikowska ◽  
Tala Tayoun ◽  
Marianna Garonzi ◽  
Genny Buson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Epithelial To Mesenchymal Transition ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Anaplastic Lymphoma

AbstractGatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer. Single CTC isolation and phenotyping were performed by DEPArray or fluorescence-activated cell sorting following enrichment and immunofluorescence staining (ALK/cytokeratins/CD45/Hoechst). CNA heterogeneity was evaluated in six ALK-rearranged patients harboring ≥ 10 CTCs/20 mL blood at resistance to 1st and 3rd ALK-TKIs and one presented gatekeeper mutations. Out of 82 CTCs isolated by FACS, 30 (37%) were ALK+/cytokeratins-, 46 (56%) ALK-/cytokeratins+ and 4 (5%) ALK+/cytokeratins+. Sequencing of 43 CTCs showed highly altered CNA profiles and high levels of chromosomal instability (CIN). Half of CTCs displayed a ploidy >2n and 32% experienced whole-genome doubling. Hierarchical clustering showed significant intra-patient and wide inter-patient CTC diversity. Classification of 121 oncogenic drivers revealed the predominant activation of cell cycle and DNA repair pathways and of RTK/RAS and PI3K to a lower frequency. CTCs showed wide CNA heterogeneity and elevated CIN at resistance to ALK-TKIs. The emergence of epithelial ALK-negative CTCs may drive resistance through activation of bypass signaling pathways, while ALK-rearranged CTCs showed epithelial-to-mesenchymal transition characteristics potentially contributing to ALK-TKI resistance. Comprehensive analysis of CTCs could be of great help to clinicians for precision medicine and resistance to ALK-targeted therapies.

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