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H.C. Freitas



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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-047 - Clinical Presentation and Outcome of Neuroendocrine Lung Tumors in a Brazilian Cohort from 2000 to 2016 (ID 5778)

      14:30 - 15:45  |  Author(s): H.C. Freitas

      • Abstract
      • Slides

      Background:
      Neuroendocrine lung tumors (NET) are rare and heterogeneous neoplasms. Typical carcinoids (TC) and atypical carcinoids (AC) have better prognosis and their treatment is mainly focused on surgery. Large cell neuroendocrine carcinomas (LCNLC) are commonly widespread at diagnosis. Here we present clinical characteristics and outcome of patients with TC, AC and LCNLC treated at AC Camargo Cancer Center (ACCCC).

      Methods:
      We selected 114 consecutive patients with TC, AC or LCNLC treated at ACCCC from 2000 to 2016. Demographic variables included individual data, diagnostic and treatment patters. Data was collected and processed to obtain outcomes and survival information. It was intended to obtain not only epidemiologic characteristics, but also to determine and confirm selected variables as prognostic.

      Results:
      Main demographic results are described in the Table below:

      VARIABLES TC AC TOTAL
      NUMBER OF PATIENTS 64(56.1%) 24(21.1%) 88(100%)
      SEX MALE 53.1% 41.7% 45.5%
      FEMALE 46.9% 58.3% 54.5%
      MEDIAN AGE YEARS 56.35 53.74 57.48
      CLINICAL STAGING I 83.9% 55.0% 76.8%
      II 4.8% 20.0% 8.5%
      III 6.5% 0.0% 4.9%
      IV 4.8% 25.0% 9.8%
      ECOG 0 71.7% 84.6% 76.4%
      ≥1 20.3% 15.4% 25.4%
      COMORBIDITIES YES 56.9% 65.2% 59.3%
      NO 75.4% 66.7% 73.1%
      SMOKING HISTORY YES 24.6% 33.3% 26.9%
      NO 75.4% 66.7% 73.1%
      OTHER MALIGNANCIES YES 32.8% 4.2% 25%
      NO 67.2% 95.8% 75%
      FAMILY HISTORY YES 59.4% 66.7% 61.4%
      NO 40.6% 33.3% 38.6%
      SURGERY YES 92.2% 79.2% 88.6%
      NO 7.8% 20.8% 11.4%
      For the entire population, median progression free survival (mPFS) was 158.5 months. mPFS was not reached (NR) for TC and AC, with 5-year PFS 81% for TC and 84% for AC and 10-year PFS 69% for TC and 59% for AC; no Statistical Significance (SS) was found between TC and AC in mPFS (p=0,549). mPFS was worst, with SS, for age ≥65 years (158.5x61.5 months; p=0.018), staging ≥2 (NRx75.7 months; p=0,027), ECOG ≥1 (158.5x35.2 months; p=0.001), node positive disease (N0xN≥1: NRx33.9; p=0.001). Same tendencies were observed for TC, also with SS, but not for AC. Median overall survival (mOS) retained the same tendency: 5-year OS was 74% for TC and 55% for AC and 10-year OS was 74% for TC and 47% for AC. mOS was not reached. Age ≥ 65 years (p=0.001), ECOG ≥1 (p=0.001) and staging ≥ 2 (p=0.001) also were predictable for worst mOS.

      Conclusion:
      This study demonstrates an epidemiologic descriptive outlook of neuroendocrine LC in a Brazilian population. Older age, worst performance and higher staging were prognostic for poor outcomes in survival.

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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-005 - Evaluation of Circulating Tumoral Microemboli (CTM) as a Prognostic Factor in Non-Small Cell Lung Cancer (NSCLC) (ID 5391)

      14:30 - 15:45  |  Author(s): H.C. Freitas

      • Abstract
      • Slides

      Background:
      Much has been studied regarding the prognostic role of circulating tumor cells (CTCs) in NSCLC. CTM (defined as clusters of 3 or more cancer cells detected in peripheral blood) relationship to prognosis was previously published for small cell lung cancer (SCLC), demonstrating worst prognosis for the presence of CTM. No relevant data, however, was published for CTM in NSCLC. The objective of this study is to define the presence of CTM as a prognostic factor for survival in NSCLC and its molecular characteristics.

      Methods:
      It was performed a retrospective evaluation of 31 metastatic NSCLC patients positive for CTC, which were previously enrolled for CTC research in a single institution. CTC and CTM were detected by ISET (Isolation by Size of Epithelial/Trophoblastic Tumor Cells, Rarecells, France®). Included patients had metastatic disease treated in multiple lines of cytotoxic treatment. Analysis included frequencies, demographic characteristics and survival variables, including Progression Free Survival (PFS) and Overall Survival (OS), with PFS as primary endpoint. The PFS and OS were calculated based on the date of first CTC collection and first progression after collection (PFS) or death (OS). Molecular characterization was performed by immunocytochemistry for Transforming Growth Factor beta receptor (TGFßR) and Matrix Metalloproteinase 2 (MMP2).

      Results:
      The primary endpoint was not met. Presence of CTM did not have statistically significant influence on PFS or OS in our population. Eight patients were positive (CTM+) and 23 were negative (CTM-) for CTM. Median follow-up was 13.3 months (m). Median age was 65.5 years in CTM- and 69.6 years in CTM+ patients. Remaining demographic variables were balanced between groups. All patients had progressive disease and 9 were still alive at the time of analysis. Median PFS (mPFS) was 6.9m for CTM- and 4,5m for CTM+, with p=0.59. Median OS (mOS) was paradoxically greater in CTM+, without statistical significance (27.3m for CTM- and 31.6m for CTM+; p=0.83). Molecular characterization did not have any prognostic impact on both CTM- and CTM+ groups. No patient was positive for TGFßR and 2 CTM+ patients were positive for MMP2 (10/31 patients with isolated CTCs positive for MMP2).

      Conclusion:
      This retrospective analysis showed no impact on survival for the presence of CTM in NSCLC, which was opposite to findings of positive prognostic value of CTM for SCLC where CTM was a negative factor for survival. Molecular characterization also did not show differences between groups. The findings warrant further evaluation in dedicated research.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-058 - Blood Cell Count Ratios at Diagnosis as Prognostic Markers in Patients with Metastatic Non-Small Cell Lung Cancer (mNSCLC) (ID 4645)

      14:30 - 15:45  |  Author(s): H.C. Freitas

      • Abstract
      • Slides

      Background:
      Systemic inflammation has been linked with cancer development and outcome. Several biomarkers reflect this inflammatory response, notably, the neutrophil (NLR), monocyte (MLR) or platelet (PLR) to lymphocyte blood count ratio. It has also been shown that inflammatory/immune cells (IC) in tumor microenvironment have an importantrole in tumor development and behavior. The aim of this study is to investigate the clinical significance of NLR,MLR, PLR and IC infiltration as prognostic factors in mNSCLC.

      Methods:
      We retrospectively collected clinical, pathological and demographical data from the medical charts of mNSCLCpatients, diagnosed between Jan 1st 2011 and July 30th 2014, from a single Brazilian institution. When available,archival tissue samples were evaluated for tumor IC intensity and pattern (hematoxylin-eosin stain)and CD8 and FOXP3 positive cell counts by immunohistochemistry (IHC).NLR, MLR and PLR were defined as the ratio between the absolute neutrophil, monocyte or platelet to lymphocyte blood counts. Overall survival (OS) was calculated from the time of CT start for metastatic disease till death by any cause. Association between clinical variables and NLR/MLR/PLR was tested with Chi-square or Fisher´s exact test. OS curves were generated by Kaplan–Meier method and compared using log-rank test. Multivariate analysis was performed using Cox regression (backward stepwise method) to assess variables independently associated with OS. P values <0.05 were considered statistically significant.

      Results:
      A total of 170 patients were included in the study.Median age was 63.4 years, 54.1% were male, 80.6% had adenocarcinoma, 17.1% had mutated EGFR, 73.3% were current/former smokers, and 78.2% had ECOG≤1. Median values for NLR, MLR and PLR were 4.6, 0.419 and 215, respectively. 114 (67.1%) patients had samples available for IC analysis and 88 for IHC, 39% had moderate to strong IC(IC2/3) infiltrate and 91.2% had a monuclear predominant infiltration pattern. Median follow-up time was 19.64 months (mo) and median overall survival was 13.6 mo. NLR>4.6 (6.89 vs. 19.05 mo, p<0.001) and PLR>215 (6.89 vs. 8.7 mo, p<0.014) were associated with poor OS. IC2/3 was associated with shorter OS (IC1 13.63mo vs. 4.6mo IC2/3, p=0.006), while mononuclear IC pattern was associated with improved survival (13.6 vs. 4.6 mo, p=0.023). CD8 and FOXP3 positive cells were not associated with OS. In multivariate analysis, the NLR remained as an independent prognostic factor for worse OS (HR 2.71 IC95% 1.39-5.25, p=0.003).

      Conclusion:
      Elevated NLR is an independent predictor of poor OS in patients with advanced NSCLC.

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