Imaging Features and Patterns of Metastasis in Non-Small Cell Lung Cancer with RET Rearrangements

Rearranged during transfection proto-oncogene (RET) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive (RET+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET+, ALK+ and ROS1+ NSCLC. Patients with RET+, ALK+, or ROS1+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET, ALK, or ROS1 gene fusion (RET = 32; ALK = 116; ROS1 = 67). Patients with RET+ NSCLC were older at presentation compared to ALK+ and ROS1+ patients (median age: RET = 64 years; ALK = 51 years, p < 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology (RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET+ patients were more likely to be peripheral (RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1+ NSCLC (RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET+ NSCLC shares several distinct radiologic features and metastatic spread with ALK+ and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.

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Imaging Features and Metastatic Patterns of Advanced ALK-Rearranged Non–Small Cell Lung Cancer

American Journal of Roentgenology ◽

10.2214/ajr.19.21982 ◽

2020 ◽

Vol 214 (4) ◽

pp. 766-774 ◽

Cited By ~ 6

Author(s):

Dexter P. Mendoza ◽

Jessica J. Lin ◽

Marguerite M. Rooney ◽

Tianqi Chen ◽

Lecia V. Sequist ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Imaging Features ◽

Small Cell Lung ◽

Metastatic Patterns

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Clinicopathologic and Imaging Features of Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

Cancers ◽

10.3390/cancers11122033 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2033 ◽

Cited By ~ 5

Author(s):

Subba R. Digumarthy ◽

Dexter P. Mendoza ◽

Eric W. Zhang ◽

Jochen K. Lennerz ◽

Rebecca S. Heist

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Imaging Features ◽

Imaging Data ◽

Small Cell Lung ◽

Clinicopathologic Characteristics ◽

Pre Treatment ◽

Metastatic Sites

MET exon 14 (METex14) skipping mutations are an emerging potentially targetable oncogenic driver mutation in non-small-cell lung cancer (NSCLC). The imaging features and patterns of metastasis of NSCLC with primary METex14 skipping mutations (METex14-mutated NSCLC) are not well described. Our goal was to determine the clinicopathologic and imaging features that may suggest the presence of METex14 skipping mutations in NSCLC. This IRB-approved retrospective study included NSCLC patients with primary METex14 skipping mutations and pre-treatment imaging data between January 2013 and December 2018. The clinicopathologic characteristics were extracted from electronic medical records. The imaging features of the primary tumor and metastases were analyzed by two thoracic radiologists. In total, 84 patients with METex14-mutated NSCLC (mean age = 71.4 ± 10 years; F = 52, 61.9%, M = 32, 38.1%; smokers = 47, 56.0%, nonsmokers = 37, 44.0%) were included in the study. Most tumors were adenocarcinoma (72; 85.7%) and presented as masses (53/84; 63.1%) that were peripheral in location (62/84; 73.8%). More than one in five cancers were multifocal (19/84; 22.6%). Most patients with metastatic disease had only extrathoracic metastases (23/34; 67.6%). Fewer patients had both extrathoracic and intrathoracic metastases (10/34; 29.4%), and one patient had only intrathoracic metastases (1/34, 2.9%). The most common metastatic sites were the bones (14/34; 41.2%), the brain (7/34; 20.6%), and the adrenal glands (7/34; 20.6%). Four of the 34 patients (11.8%) had metastases only at a single site. METex14-mutated NSCLC has distinct clinicopathologic and radiologic features.

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[18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non–Small Cell Lung Cancer

Tomography ◽

10.18383/j.tom.2018.00026 ◽

2019 ◽

Vol 5 (1) ◽

pp. 145-153 ◽

Cited By ~ 7

Keyword(s):

Lung Cancer ◽

Positron Emission Tomography ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Emission Tomography ◽

Imaging Features ◽

Small Cell Lung ◽

Positron Emission ◽

18F Fdg

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Fragmentation of Small-cell Lung Cancer Regulatory States in Heterotypic Microenvironments

10.1101/2020.03.30.017210 ◽

2020 ◽

Cited By ~ 2

Author(s):

Dylan L. Schaff ◽

Shambhavi Singh ◽

Kee-Beom Kim ◽

Matthew D. Sutcliffe ◽

Kwon-Sik Park ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Single Cell ◽

Cell Lung Cancer ◽

Small Cell ◽

Neuroendocrine Cells ◽

Fluctuation Analysis ◽

Alveolar Type ◽

Small Cell Lung ◽

Primary Tumors

AbstractSmall-cell lung cancers derive from pulmonary neuroendocrine cells, which have stemlike properties to reprogram into other cell types upon lung injury. It is difficult to uncouple the plasticity of these transformed cells from heritable changes that evolve in primary tumors or select in metastases to distant organs. Approaches to single-cell profiling are also problematic if the required sample dissociation activates injury-like signaling and reprogramming. Here, we defined cell-state heterogeneities in situ through laser capture microdissection-based 10-cell transcriptomics coupled with stochastic-profiling fluctuation analysis. Using labeled cells from a small-cell lung cancer mouse model initiated by neuroendocrine deletion of p53 and Rb, we profiled cell-to-cell transcriptional-regulatory heterogeneity in spheroid cultures and liver colonies seeded intravenously. Fluctuating transcripts in vitro were partly shared with other epithelial-spheroid models, and candidate heterogeneities increased considerably when cells were delivered to the liver. Colonization of immunocompromised animals drove the fractional appearance of alveolar type II-like markers and poised cells for paracrine stimulation from immune cells and hepatocytes. Immunocompetency further exaggerated the fragmentation of tumor states in the liver, yielding mixed stromal signatures evident in bulk sequencing from autochthonous tumors and metastases. We identified dozens of transcript heterogeneities that recur irrespective of biological context; their mapped orthologs brought together observations of murine and human small-cell lung cancer. Candidate heterogeneities recurrent in the liver also stratified primary human tumors into discrete groups not readily explained by molecular subtype. We conclude that heterotypic interactions in the liver and lung are an accelerant for intratumor heterogeneity in small-cell lung cancer.Statement of significanceThe single-cell regulatory heterogeneity of small-cell lung cancer becomes increasingly elaborate in the liver, a common metastatic site for the disease.

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P1.01-041 Quantitative Imaging Features Predict Response of Immunotherapy in Non-Small Cell Lung Cancer Patients

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2016.11.565 ◽

2017 ◽

Vol 12 (1) ◽

pp. S474-S475 ◽

Cited By ~ 2

Author(s):

Ilke Tunali ◽

Jhanelle Gray ◽

Jin Qi ◽

Mahmoud Abdullah ◽

Yoganand Balagurunathan ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Quantitative Imaging ◽

Small Cell ◽

Imaging Features ◽

Small Cell Lung ◽

Lung Cancer Patients

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Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy

Bioscience Reports ◽

10.1042/bsr20182082 ◽

2019 ◽

Vol 39 (7) ◽

Author(s):

Xue Yang ◽

Gaopei Meng

Keyword(s):

Lung Cancer ◽

Liver Metastasis ◽

Tumor Growth ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Tumor Xenograft ◽

Small Cell Lung ◽

Primary Tumors ◽

Ifn Γ

Abstract In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.

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