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Andres Castro



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-37 - Biomarkers in Non-Small Cell Lung Cancer: Expression of PD-L1 Protein and p16 in Squamous Cell Carcinoma Histologic Subtype (ID 2773)

      08:00 - 18:00  |  Author(s): Andres Castro

      • Abstract
      • Slides

      Background

      Squamous cell carcinoma(SCC), 30% of Non-Small Cell Lung Cancer(NSCLC), cigarette is its mayor etiology. >50% NSCLC are diagnosed in advanced/stage, 10–15%EIIIB, 40%E-IV. In terms of survival, NSCLC is heterogeneous and variable. Survival at 5 years is <15%, treatment is not curative.

      In cancer, the evasion of the immune system and the uncontrolled tumor proliferation is important. The programmed-cell-death-ligand(PD-L1) is a lymphocyteT protein. The union PD-1/PD-L1 inhibits the lymphocyteT’s activity. Overexpression of PD/L1 in CD8+lymphocytes inhibits apoptosis, reduces survival. In NSCLC, PD-L1 is a predictor of successful immunotherapy. Inhibition PD:PD-L1 is an effective antitumoral therapy.

      The p16INK4a intervenes in pulmonary carcinogenesis, localized in chromosome 9p21(locus CDKN2A), its codes suppressor/tumoral proteins:p16INK4a-p14ARF. P16 inhibits D1-dependent quinases4-6(CDK4/6,ciclinaD1) which regulate the retinoblastoma protein through phosphorylation. Dysfunctional p16 inactivates Rb through hyperphosphorilation and progression of the cell cycle. Its expression contributes to the therapeutic response and to survival in NSCLC. We describe the clinical, pathological and survival characteristics in SCC based in expression of PD-L1/p16.

      Method

      Descriptive study, 24 patients with SCC, 2009–2013. PD–L1 studied with antibody 22C3 pharmDxkit(Agilent,Santa-Clara,CA,USA) in Autostainer Link/48DAKO®with murine monoclonal antibody(Clone/E6H4™) in BenchMark/Autostainer(Ventana®). PD-L1 was classified with TPS(Tumor/Proportion/Score), high expression TPS>50%, low expression TPS1-49%, or negative TPS=0%. P16(+) with expression >70% in nuclei, tumoral membranes.

      STATAv.14®, ShapiroWilk, Chi squared, Fisher, t-Student or U/Mann/Whitney were used. Survival with Kaplan-Meier.

      Result

      Age 67+14, 63%men. 54% of smokers, 7% had COPD. E-IV54%, E-IIIA25%, E-IIIB13%, E-IIB y E-IIA4%. PD-L1(+) more in smokers (85%)p=0.001. Treatment: palliative/care(25%), chemotherapy/surgery(17%); chemotherapy/radiotherapy/surgery(12%); radiotherapy/surgery(8%), only surgery(4%). PD-L1, high-expression survival 33m, low expression/negative 66m (log-rank test p=0.0041), Figure1: p16(+) in 10(41.6%), survival 36.2m, p16(-) survival 66.8m, p16/PD-L1(-) survival 66.8m, p16/PD-L1(+) survival 36.2m.

      Conclusion

      SCC with PD-L1 TPS>=50%, p16(+), smokers with high/tumor/burden had lower survival rates.

      Immunotherapy against programmed cell death(PD-1) is a promising alternative impacting survival in advanced/metastatic NSCLC.

      pd-l1 y p16 iaslc 2019.png

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    EP1.05 - Interventional Diagnostics/Pulmonology (ID 195)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.05-02 - Endobronchial Ultrasound and Transbronchial Needle Aspiration EBUS-TBNA: In a University Hospital in Latin America (ID 2729)

      08:00 - 18:00  |  Author(s): Andres Castro

      • Abstract
      • Slides

      Background

      Endobronchial Ultrasound and Transbronchial Needle Aspiration (EBUS-TBNA) nowadays it has a primordial role in the workup of malignant and nonmalignant pulmonary disease. It’s the most important advancement in pulmonary medicine in the last 20 years.EBUS-TBNA is a minimally invasive technique, well tolerated, cost efficient, for real time visualization of the airways with ultrasound and for sampling the mediastinum and hilum. Its indications: diagnosis, staging, restaging of lung cancer, evaluation of metastatic lesions and non-malignant diseases. It requires multidisciplinary evaluation with image analysis, general condition of the patient, risks and benefits, also close work with pathology, performing a Rapid On-Site Evaluation (ROSE) to improve the diagnostic performance.

      We describe the EBUS-TBNA in Fundación Valle del Lili a University Hospital of Reference in Latin America.

      Method

      Prospective, descriptive study, period June/2015-June/2018. The indications were staging and restaging of lung tumors, diagnosis of lung or mediastinal masses, abnormal ganglia in CT or PET/CT equal or greater than 1cm. 108 patients were evaluated under general IV anesthesia, with a standardized protocol in the endoscopy room. The equipment used was Olympus® bronchoscope + US probe + 22G FNA.

      Result

      Average age of 63,5 +/- 12,9, women 53(49%), men 55(50,9%)
      The quality of the sample was adequate in 105 (97,22%), positive of malignity 63(60%) negative 42(40%), inadequate samples 2(1,8%) and in one case a complete evaluation of the mediastinum was made without evidence of lesions, so no samples were taken. The ganglionary stations most frequently evaluated were 7 40(37%), 11R 22(20,3%), 11L 14(12,9%) and mediastinal mases 11(10,1%).

      The malignant lesions were non-small cell pulmonary carcinoma (NSCLC) 26(41,2%), metastasis head and neck tumors 10(15,8%), small cell pulmonary carcinoma 9(14,28%).

      97,22% of the smears with Diff-Quick staining presented lesion, 5 dips were performed in each station, and immunohistochemistry was made in cellblocks as well as DNA extraction for EGFR mutation studies and EML4/ALK gene rearrangements in 50% of cases of NSCLC and PDL1 in 19,2% of these cases. 10(9,26%) of the series was taken to mediastinoscopy with a 100% correlation with the results of EBUS-TBNA.

      Conclusion

      EBUS-TBNA is the recommended technique for lung cancer mediastinal staging. Our results adjust to international results; it is safe, minimally invasive, in many cases an outpatient procedure and a good performance when accompanied with ROSE.

      table 1 ebus-tbna.png

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      EP1.05-03 - Therapeutic Bronchoscopy in Multimodal Therapy for the Management of Central Airway Obstruction (ID 2799)

      08:00 - 18:00  |  Author(s): Andres Castro

      • Abstract
      • Slides

      Background

      Central airway obstruction may be due to malignant and non-malignant causes. The malignant obstruction of the airway is an important cause of morbidity and mortality in lung cancer. Intervention with therapeutic bronchoscopy decreases symptoms and allows time to employ treatments like surgery/radiotherapy or quimotherapy. In benign pathology prior intubation or complications related to lung/transplantation are common. Patients usually have cough and dyspnea that can progress to respiratory failure. Therapy should be oriented to secure and restore the airway. Best technique choice depends on etiology, type and severity of lesion, technological availability and operators skills. Nowadays, a multimodal therapy is implemented, including different intervention methods for the management. We aimed to describe therapeutic bronchoscopy in Fundación Valle del Lili a University Hospital in Latin America.

      Method

      Descriptive retrospective study, April-2013/June-2018. 151 procedures were performed. Symptoms, etiology, localization, severity, diagnosis, type of anesthesia, interventions and complications were analyzed. The device was a therapeutic flexible and rigid bronchoscope Olympus® and specific intervention instruments.

      Result

      56.9+/-16.9-years. 58(38%)women and 93(61,5%)men. Malignant lesions were found in 91(60.26%). Symptoms were cough 122(80.8%), dyspnea 122(80.8%), hemoptysis 51(33.8%) and chest pain 41(27.2%). General anesthesia was used in 147(97.35%), the most common approach was the use of laryngeal mask 112(74,17%) then an endotracheal tube 22(14.57%). In 108(71,52%) a severe airway obstruction was present. 93(61,59%) had an endobronchial mass and 36(23,84%) external compression. Lesion location was: left-stem bronchi 73(48,34%) right-stem bronchi 64(42,38%), trachea inferior 23(15,23%), trachea superior 18(11,92%), carina 18(11,92%), trachea media 11(7,28%) and intermediate bronchus 11(7,28%). Most common malignant etiology was non-small cell lung cancer 39(42,85%), followed by typical/atypical carcinoid tumor 11(12,08%), sarcoma 9(9,89%) and metastatic tumors of gastrointestinal origin 8(8,79%) and head and neck tumors 6(6,59%) among others. Benign pathology was found in 60(39,7%) included granuloma 11(18,33%), stenosis 41(68,3%) which are related in most with airway complications after lung/transplantation and foreign bodies were found in 6(10%). Procedures were debridement 104(68,87%), electrocoagulation 95(62,91%), argon plasma 39(25,83%), stent colocation 5(3,31%), balloon/dilatation 42(27,81%) and cryoprobe 29(19,21%). Multiple interventions were made in various patients. Obstruction resolution was complete for 56(37,09%) and there was residual stenosis in 42(27,81%) or residual mass in 53(35,1). Complications included mild hemoptysis in 8(5,38%) and scaling in the attention room in two cases. No reported deaths associated with the procedure.

      Conclusion

      Central airway obstruction is a complex situation that requires multidisciplinary approach. Currently, multimodal therapy is recommended combining different options of intervention, through flexible or rigid bronchoscopy, to achieve optimal results.

      figure 1. therapeutic bronchoscopy.png

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