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O. Macedo



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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-014 - The Gene-Expression Profiles in advanced lung Adenocarcinoma associated with Wood Smoke or tobbacco exposure are different in brain metastasis (ID 1970)

      09:30 - 09:30  |  Author(s): O. Macedo

      • Abstract

      Background
      Environmental factors contributed toward lung carcinogenesis. Tobacco-smoking is the major etiological factor related with lung cancer in 90% in the world compared with Mexico with 66% of cases. In previous works we have demonstrated that other factors such as chronic exposure to wood smoke (WSE) are related to non-small-cell lung cancer (NSCLC) and it´s clinically and pathologically different from lung cancer arisen from tobacco-exposure, regarding on tumor histology, mutation profiles, brain metastasis incidence, response rate and overall survival. This work is aimed to estimate expression profiles related WSE on adenocarcinoma histology associated to pathological mechanisms that differ from other carcinogenic factors, such as tobacco exposure.

      Methods
      This study used clinical, longitudinal, prospective and observational. From January 2008 to June 2011, patients were admitted in Cancerology Institute with lung adenocarcinoma in stage IV, eligible for the inclusion. Clinical variables, WSE, gender and age. WSE was defined to being exposed to fumes by burning wood in fireplaces and wood stoves for five years for at least 4 hours per day. The WSE index was calculated multiplying the number of daily hours exposed by years of exposure. Collaboration agreements with the Institute of Medical Genomics and approved within the Health Research Sectorial Fund, CONACyT-México (SALUD-2009-01-115552). Primary biopsies were taken by guided tru-cut needle by tomography. Samples were analyzed by the Pathology for histological/quantification of neoplasic celularity, and stored at -80°C. RNA was extracted from tumor biopsies. RNA integrity (RIN>6) was analyzed using the Agilent 6000. We used an Affymetrix Human GeneChip® 1.0 ST. Two-Cycle Target Labeling was followed for microarrays. Analysis was done by Affymetrix console and “R” software language. Matrices employ 29 microarrays with experimental contrasts. Differential expressed genes were analyzed by linear model that analyze contrasts between experimental contrasts. The Partek Genomic Software 4 and SAM (Significant Analysis) was used for microarray comparisons and integration of genomic data.

      Results
      Using computational genomics using fold changes and confiability data we found differences in genomic expression. In brain metastasis (BM) patients the Fold Change values >1 shows 6 upregulated and 11 downregulated genes compared with or without WSE. Patients without BM the Fold Change values >1 shows 90 downregulated and 7 upregulated genes with or without WSE. Prior both analysis were confirmed with B statistics data (significant value ≥0). No difference were found using computational Genomics SAMS (False discovery rate), neither PARTEK (p-value, fold change), on gene expression evaluation.

      Conclusion
      Our results demonstrate that gene expression profiles are different in advanced lung adenocarcinoma patients with brain metastasis with or without WSE. These results could be used for predictive models related with BM in advanced lung cancer. The best genomic statistical value was obtained with Affymetrix console and “R” software language in this work. These results must be confirmed by increasing the experimental samples and validating in an independent cohort by PCR.

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    P1.16 - Poster Session 1 - Other Thoracic Malignancies (ID 186)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P1.16-004 - Pleural Solitary Fibrous Tumor: a case series (ID 3402)

      09:30 - 09:30  |  Author(s): O. Macedo

      • Abstract

      Background
      Solitary fibrous tumors are rare neoplasm arising in the visceral pleura. Despite that most of them are known to have a benign course, caution is advocated because of their unpredictable clinical behavior. Surgery is the best treatment approach and longer survival is associated with complete resection.

      Methods
      Retrospective review from January 2005 to december 2012 for patients with diagnosis of pleural solitary fibrous tumor. Demographic and tumor variables were analyzed.

      Results
      Seven patients were treated at the National Cancer Institute in Mexico City with the clinical impression of a rare thoracic tumour. There were 5 females and 2 males with a mean age of 51.42 years old. After discarding other pleural and pulmonar malignancies, surgery was the only treatment modality used in the series with a curative intention. Tumorectomy with negative macroscopic margin was performed in 4 patients, a thoracoscopic wedge resection was performed in 1 patient, ; and 1 patient with a voluminous tumor required a pleuro-pneumonectomy to achieve a negative margin. One patient received only best supportive care because of the advanced of his disease and low performance status.. Resection was made by thoracotomy in 6 patients and only one patient was treated with thoracoscopy. The mean size of the primary tumour was 10.44 cm.. Median follow up was of 18 months (mean 42.4 months, range 3-158 months). Two patients developed a thoracic recurrence which could not be controlled with surgical resection and received only best supportive care.

      Conclusion
      Due to the rarity of this tumor there are no many tretament options. Most of this neoplasms have an indolent course with diagnosis only after they became larger and symptomatic. Complete surgical resection is by far the best chance for cure. However, in case of malignant solitary fibrous tumors, there are no established systemic therapy alternatives, either preoperatively or postoperatively.

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    P3.16 - Poster Session 3 - Other Thoracic Malignancies (ID 188)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P3.16-003 - Overall Survival and Surgical Outcomes for Mediastinal germ-cell tumors: The National Cancer Institute of Mexico experience. (ID 3361)

      09:30 - 09:30  |  Author(s): O. Macedo

      • Abstract

      Background
      Extragonadal germ-cell are rare, most of them arising in the anterior mediastinum and comprise less than 5% of all germ-cell malignancies, Although they also occur in women, the men are the most affected. This tumors are considered with a worse prognosis than their primary gonadal counterparts. Standar treatment includes chemotherapy with bleomycin, etoposide and cisplatin, sometimes followed by surgery. Five-year overall survival is about 45%

      Methods
      Retrospective, single institution review from January 2005 to december 2012. We included patients with mediastinal germ-cell tumors treated with chemotherapy plus surgery. We reviewed patient characteristics to identify factors associated with overall survival.

      Results
      We included 28 patients in the final analysis, there were 25 males (89.3%) and 3 females (10.7%), mean age 26.71 years (range 15 -39 years). Mediastinal tumor and elevated serum tumor markers were present in 22 patients; in 6 patients a pre-treatment biopsy was needed because serum tumor markers were negative. Non-seminomaotus germ-cell tumor was diagnosed in 22 patients, seminoma in 2 patients and mature teratoma in 4 patients. Except for the teratoma patients, all received preoperative chemotherapy, BEP regimen was used in 53.6% of patients. A second line of chemotherapy was used in 8 patients (28.6%) and only 1 patient received a third line of chemotherapy. Serum tumor markers prior to surgery were negative in 19 patients, meanwhile 9 patients underwent surgery with positive serum tumor markers. Surgical approach was made by median esternotomy in 15 patients, and posterior thoracotomy in 11 patients. Extensive resections (including lung resection and/or pericardial resection and/or bone resection) were performed in 16 patients. Perioperative mortality was 3.6% (one pneumonectomy patient). Median size tumor was 13.3 cm (range 4-25 cm) Complete resection was achieved in 23 patients (82.1%). Pathology in surgical specimens were viable germ-cell tumor in 12 patients (42.9%), mature teratoma in 6 patients (23.4%), inmature teratoma in 4 patients (14.3%) , necrosis in 4 patients (14.3%) and seminoma in 2 patients (7.1%). Only 7 patients (25%) received an additional line of postoperative chemotherapy. Median overall survival was 18.32 months (range 1-102 months). Seminoma and teratoma were associated with longer survival, meanwhile in non-seminoatous tumors preoperative negative serum tumor markers showed a better prognosis.

      Conclusion
      Surgical outcomes have improved over time with a positive impact in overall survival. Although the prognosis still worse for this subgroup of patients with extragonadal germ-cell tumors, our results indicates that a proper selection with agressive surgery entitles a better prognosis with low mortality. Factors associated with better survival were histology, serum tumor markers status prior to surgery and pathologic report of the surgical specimen.