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1.
Cell ; 182(5): 1232-1251.e22, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32822576

ABSTRACT

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.


Subject(s)
Lung Neoplasms/genetics , Biomarkers, Tumor/genetics , Cell Line , Ecosystem , Humans , Lung Neoplasms/pathology , Macrophages/pathology , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , T-Lymphocytes/pathology , Tumor Microenvironment/genetics
2.
J Vasc Interv Radiol ; 30(4): 589-593.e3, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30910181

ABSTRACT

Opportunities for interventional radiology (IR) education and exposure remain limited at medical institutions without a local IR presence, thereby excluding a medical student population with potential to pursue careers in IR or become referring providers to IR. The purpose of this study was to evaluate the efficacy of a Webinar-based IR elective as an educational tool for outreach to US medical schools lacking local preclinical IR exposure. Our early results indicate that a Webinar-based IR lecture series can serve as an effective method for educating future physicians about the field of IR and when to consult IR for patient management.


Subject(s)
Career Choice , Computer-Assisted Instruction/methods , Education, Medical, Undergraduate/methods , Internet , Radiologists/education , Radiology, Interventional/education , Specialization , Students, Medical , Curriculum , Female , Humans , Male
3.
J Vasc Interv Radiol ; 26(10): 1472-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26296737

ABSTRACT

PURPOSE: To identify imaging findings associated with elevated lung shunt fraction (LSF) in patients being considered for yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: During the period 2009-2014, 152 consecutive patients underwent planning hepatic arteriography with technetium-99m ((99m)Tc) macroaggregated albumin (MAA) injection. Computed tomography (CT) or magnetic resonance imaging performed before the procedure for each patient was assessed for hepatic vein (HV) tumor thrombus or occlusion from external compression by tumor. When imaging was a multiphase CT scan (117 patients), the arterial phase was evaluated for evidence of early HV opacification (relative to unaffected HVs), indicating hepatic venous shunting. These factors were correlated with LSF determined by (99m)Tc-MAA imaging. RESULTS: Median LSF was 6.7% (range, < 0.1%-71%), significantly higher for HCC (8.0% vs 6.3% for other tumors, P = .048). Larger tumor size was associated with higher LSF in univariate analysis (P = .001). There was high interobserver agreement for determining hepatic venous shunting (97%, κ = 0.847), which was associated with higher LSF (P < .001; 78% sensitivity, 93% specificity). Of 5 cases of HV tumor thrombus, all had high (> 20%) LSF (P < .001). HV occlusion was also associated with higher LSF (P = .039). Multivariate analysis confirmed that early HV opacification and either HV tumor thrombus or occlusion were associated with higher LSF. CONCLUSIONS: Early HV opacification and HV tumor thrombus or occlusion on cross-sectional imaging performed before radioembolization are associated with elevated LSF, which may contraindicate or limit the dose delivered in (90)Y radioembolization. This information could be helpful during patient counseling for anticipating the most appropriate mode of liver-directed therapy.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Hepatic Veins/diagnostic imaging , Liver Neoplasms/radiotherapy , Lung/radiation effects , Radiotherapy, Image-Guided/methods , Yttrium Radioisotopes/therapeutic use , Absorption, Radiation , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnostic imaging , Female , Humans , Liver Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Male , Middle Aged , Organs at Risk/radiation effects , Patient Selection , Prognosis , Radionuclide Imaging , Radiopharmaceuticals/therapeutic use , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome
4.
J Vasc Interv Radiol ; 24(4): 566-71, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23462065

ABSTRACT

PURPOSE: To compare the frequency of vena caval penetration by the struts of the Option and Günther Tulip cone filters on postplacement computed tomography (CT) imaging. MATERIALS AND METHODS: All patients who had an Option or Günther Tulip inferior vena cava (IVC) filter placed between January 2010 and May 2012 were identified retrospectively from medical records. Of the 208 IVC filters placed, the positions of 58 devices (21 Option filters, 37 Günther Tulip filters [GTFs]) were documented on follow-up CT examinations obtained for reasons unrelated to filter placement. In cases when multiple CT studies were obtained after placement, each study was reviewed, for a total of 80 examinations. Images were assessed for evidence of caval wall penetration by filter components, noting the number of penetrating struts and any effect on pericaval tissues. RESULTS: Penetration of at least one strut was observed in 17% of all filters imaged by CT between 1 and 447 days following placement. Although there was no significant difference in the overall prevalence of penetration when comparing the Option filter and GTF (Option, 10%; GTF, 22%), only GTFs showed time-dependent penetration, with penetration becoming more likely after prolonged indwelling times. No patient had damage to pericaval tissues or documented symptoms attributed to penetration. CONCLUSIONS: Although the Günther Tulip and Option filters exhibit caval penetration at CT imaging, only the GTF exhibits progressive penetration over time.


Subject(s)
Vascular System Injuries/etiology , Vena Cava Filters/adverse effects , Vena Cava, Inferior/injuries , Wounds, Penetrating/etiology , Adult , Aged , Aged, 80 and over , Device Removal , Female , Humans , Male , Middle Aged , Phlebography/methods , Prosthesis Design , Retrospective Studies , Risk Factors , Time Factors , Tomography, X-Ray Computed , Vascular System Injuries/diagnostic imaging , Vascular System Injuries/therapy , Vena Cava, Inferior/diagnostic imaging , Wounds, Penetrating/diagnostic imaging , Wounds, Penetrating/therapy , Young Adult
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