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133P PULMONARY METASTASECTOMY – A SINGLE INSTITUTION EXPERIENCE
S56 responses, progression free survival, adverse events and quality of life functions. Results: Out of the 27 patients 13 were males and 14 females. Both arms were well matched for disease stage, performance status and age. In the Lapatinib arm, 8/13 patients (61.5%) had partial response and 2/13 patients (15.3%) had stable disease. 3/13 patients (23%) had progressive disease. In chemotherapy-only arm 5/14 patients had partial response (36%) while 3/14 patients (21%) had stable disease. 6/14 patients (43%) had progressive disease. The partial response rates were significantly more in Lapatinib arm (p = 0.03) while partial response plus stable disease were not significantly different between two arms (p = 0.3). The median disease free survival was significantly more in Lapatinib arm than the chemotherapy-only arm (7.8 months vs 5.5 months) (p = 0.02). Median overall survival was not reached in either arm. The treatment was well tolerated in both the arms with no major skin rash and cardiotoxicity seen with Lapatinib Conclusions: There is a good rationale to use dual blockade of Her2 and EGFR along with chemotherapy in NSCLC. As found in this study, it may translate into better tumor responses and even better survival especially in never or seldom smokers. This hypothesis needs to be tested in large multicenter trials.
132PD IMMUNE REGULATORY EFFECTS OF SIMVASTATIN IN REGULATORY T CELLS MEDIATED TUMOR IMMUNE TOLERANCE S.Y. Lee1 , H.K. Choi1 , J.Y. Moon1 , G.Y. Hur1 , J.H. Kim2 , C. Shin3 , J.J. Shim1 , K.H. In4 , S.H. Yoo4 , K.H. Kang1 1 Internal Medicine, Guro Hospital Korea University, Seoul, Korea, 2 Department of Internal Medicine, Korea University Medical Center, Ansan, Korea, 3 Internal Medicine, Ansan Hospital Korea University, Ansan, Korea, 4 Internal Medicine, Anam Hospital Korea University, Seoul, Korea Background: Statins are potent inhibitors of HMG-CoA reductase and are emerging as potentially interesting anticancer agents based on the preclinical evidence of their anti-proliferative, proapoptotic and anti-invasive properties. In particular, compelling evidence exists that statins have extensive immune modulatory properties; however, little is known about their relation with tumor immune tolerance. Tumor related immune tolerance involves immunosuppressive molecules produced by tumors, such as IL-10 and indoleamine-2,3-dioxygenase (IDO), which induce a regulatory T cell (Treg) response. Therefore, we investigated the effects of simvastatin on the production of IL-10, IDO production and the proliferation of Treg cells. Methods: Lewis lung cancer cells (3LL), A549, NCI-H292 lung cancer cells and Treg cells were treated with various concentrations of simvastatin for a proliferation (MTT) and IL-10 ELISA assay. The 3LL cells were inoculated into syngenic C57Bl/6 mice. Forty mice were randomized into a normal control group, a 3LL inoculated control group and a low and high dose of a simvastatin treated 3LL inoculated mice groups (N = 10 per group). The tumor mass and spleen were removed for isolation of tumor infiltrating lymphocytes (TIL) and Treg cells. We checked the expression pattern of immune regulatory markers such as IDO and Foxp3 by western blot analysis and real time PCR. Results: The proliferation of 3LL, A549 and NCI-H292 were decreased in the presence of simvastatin in a dose-dependent manner. However, simvastatin did not influence on the proliferation of Treg cells. For immune regulatory markers, IL-10 production of 3LL, A549, and NCI-H292 cells increased after treatment with simvastatin in a dose-dependent manner. Moreover, both the expression of IDO and Foxp3 are increased in 3LL and TIL, respectively. However significant differences in tumor growth rates
Advanced NSCLC were not observed between the untreated 3LL tumor control group and simvastatin treated groups. Conclusions: The results reveal that simvastatin has an antiproliferative effect on 3LL, A549 and NCI-H292 cells. However, in immune tolerance, simvastatin facilitates the immune tolerogenic potential. Especially, the facilitated immune tolerance is mediated by the increased activity of IL-10, IDO and Tregs. In summary, although simvastatin has anti-proliferative effect, it also has immune tolerogenic potentials of tumor development. 133P PULMONARY METASTASECTOMY A SINGLE INSTITUTION EXPERIENCE S. Dilege, S. Tanju, M. Saricam, S. Erus, A. Toker Thoracic Surgery, Istanbul University Istanbul Medical School, Istanbul, Turkey Background: Surgical resection is an accepted approach for patients with metastatic disease in multimodality treatment. The aim of this study is to analyse the patients who had pulmonary metastasectomy. Methods: From February 1991 to December 2008, three hundred and nineteen thoracic metastasectomy were performed over an 7-year period for 250 patients with pulmonary metastases. The patients were analysed in terms of pre-perioperative data and survival. Results: The study included 135 male, 115 female patients with a mean age of 42 years. Histopathologic types of primary tumor are epithelial in 92, sarcoma in 126 and other types in 32 patients. Forty-four patients had remetastasectomy. Median DFI and survival were in 24 and 17 months in epithelial tumors; 13 and 20 months in sarcoma and 14 and 24 months in other types respectively. Conclusions: Pulmonary metastasectomy could be performed as an additional treatment and also curative intent for chemoresistant disease. 134P PROGNOSTIC FACTORS FOR SURVIVAL IN ADULT PATIENTS (PTS) WITH METASTATIC NON-SMALL CELL LUNG CANCER AFTER THE FIRST-LINE CHEMOTHERAPY R. Belbaraka1 , O. Tr´ edan2 , A. Bajard2 , G. Chvetzoff2 , 2 I. Ray-Coquard , T. Bachelot2 , H. Errihani1 , P. Rebattu2 1 Medical Oncology, National Institute of Oncology, Rabat, Morocco, 2 Medical Oncology, Centre L´ eon B´ erard, Lyon, France Background: Little is known about prognosis of metastatic pts after first-line treatment failure. Our group has already shown that performance status (PS) > 2 and LDH > 600 UI/L were independent prognostic factors in previously treated pts enrolled in phase I clinical trials (Bachelot et al. Ann Oncol. 2000). Here, we present results from a prospective study to identify clinical and biological variables as outcome predictors. Methods: We included 45 pts previously treated for metastatic disease from 12/2000 to 11/2005 in comprehensive cancer centre (Centre L´ eon B´ erard). Clinical assessment and blood parameters were recorded. Candidate prognostic factors for overall survival (OS) with a 0.05 significance level in univariate analysis were entered in a multivariate Cox model. Results: Median age was 58.5y (range: 37 76). 62 percent of the pts were PS = 0 or 1. After inclusion pts received second-line (22.5%), third-line (5%) chemotherapy. Median follow-up and median OS were 12 months and 6 months respectively. In univariate analysis, factors associated with short OS were PS > 2, weight loss >10% and abnormal blood parameters: hemoglobin (Hb), platelet counts and IL6. The self-assessment by pts of the quality of life was not significantly correlated with OS. Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for short OS. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively.
132PD IMMUNE REGULATORY EFFECTS OF SIMVASTATIN IN REGULATORY T CELLS MEDIATED TUMOR IMMUNE TOLERANCE S.Y. Lee1 , H.K. Choi1 , J.Y. Moon1 , G.Y. Hur1 , J.H. Kim2 , C. Shin3 , J.J. Shim1 , K.H. In4 , S.H. Yoo4 , K.H. Kang1 1 Internal Medicine, Guro Hospital Korea University, Seoul, Korea, 2 Department of Internal Medicine, Korea University Medical Center, Ansan, Korea, 3 Internal Medicine, Ansan Hospital Korea University, Ansan, Korea, 4 Internal Medicine, Anam Hospital Korea University, Seoul, Korea Background: Statins are potent inhibitors of HMG-CoA reductase and are emerging as potentially interesting anticancer agents based on the preclinical evidence of their anti-proliferative, proapoptotic and anti-invasive properties. In particular, compelling evidence exists that statins have extensive immune modulatory properties; however, little is known about their relation with tumor immune tolerance. Tumor related immune tolerance involves immunosuppressive molecules produced by tumors, such as IL-10 and indoleamine-2,3-dioxygenase (IDO), which induce a regulatory T cell (Treg) response. Therefore, we investigated the effects of simvastatin on the production of IL-10, IDO production and the proliferation of Treg cells. Methods: Lewis lung cancer cells (3LL), A549, NCI-H292 lung cancer cells and Treg cells were treated with various concentrations of simvastatin for a proliferation (MTT) and IL-10 ELISA assay. The 3LL cells were inoculated into syngenic C57Bl/6 mice. Forty mice were randomized into a normal control group, a 3LL inoculated control group and a low and high dose of a simvastatin treated 3LL inoculated mice groups (N = 10 per group). The tumor mass and spleen were removed for isolation of tumor infiltrating lymphocytes (TIL) and Treg cells. We checked the expression pattern of immune regulatory markers such as IDO and Foxp3 by western blot analysis and real time PCR. Results: The proliferation of 3LL, A549 and NCI-H292 were decreased in the presence of simvastatin in a dose-dependent manner. However, simvastatin did not influence on the proliferation of Treg cells. For immune regulatory markers, IL-10 production of 3LL, A549, and NCI-H292 cells increased after treatment with simvastatin in a dose-dependent manner. Moreover, both the expression of IDO and Foxp3 are increased in 3LL and TIL, respectively. However significant differences in tumor growth rates
Advanced NSCLC were not observed between the untreated 3LL tumor control group and simvastatin treated groups. Conclusions: The results reveal that simvastatin has an antiproliferative effect on 3LL, A549 and NCI-H292 cells. However, in immune tolerance, simvastatin facilitates the immune tolerogenic potential. Especially, the facilitated immune tolerance is mediated by the increased activity of IL-10, IDO and Tregs. In summary, although simvastatin has anti-proliferative effect, it also has immune tolerogenic potentials of tumor development. 133P PULMONARY METASTASECTOMY A SINGLE INSTITUTION EXPERIENCE S. Dilege, S. Tanju, M. Saricam, S. Erus, A. Toker Thoracic Surgery, Istanbul University Istanbul Medical School, Istanbul, Turkey Background: Surgical resection is an accepted approach for patients with metastatic disease in multimodality treatment. The aim of this study is to analyse the patients who had pulmonary metastasectomy. Methods: From February 1991 to December 2008, three hundred and nineteen thoracic metastasectomy were performed over an 7-year period for 250 patients with pulmonary metastases. The patients were analysed in terms of pre-perioperative data and survival. Results: The study included 135 male, 115 female patients with a mean age of 42 years. Histopathologic types of primary tumor are epithelial in 92, sarcoma in 126 and other types in 32 patients. Forty-four patients had remetastasectomy. Median DFI and survival were in 24 and 17 months in epithelial tumors; 13 and 20 months in sarcoma and 14 and 24 months in other types respectively. Conclusions: Pulmonary metastasectomy could be performed as an additional treatment and also curative intent for chemoresistant disease. 134P PROGNOSTIC FACTORS FOR SURVIVAL IN ADULT PATIENTS (PTS) WITH METASTATIC NON-SMALL CELL LUNG CANCER AFTER THE FIRST-LINE CHEMOTHERAPY R. Belbaraka1 , O. Tr´ edan2 , A. Bajard2 , G. Chvetzoff2 , 2 I. Ray-Coquard , T. Bachelot2 , H. Errihani1 , P. Rebattu2 1 Medical Oncology, National Institute of Oncology, Rabat, Morocco, 2 Medical Oncology, Centre L´ eon B´ erard, Lyon, France Background: Little is known about prognosis of metastatic pts after first-line treatment failure. Our group has already shown that performance status (PS) > 2 and LDH > 600 UI/L were independent prognostic factors in previously treated pts enrolled in phase I clinical trials (Bachelot et al. Ann Oncol. 2000). Here, we present results from a prospective study to identify clinical and biological variables as outcome predictors. Methods: We included 45 pts previously treated for metastatic disease from 12/2000 to 11/2005 in comprehensive cancer centre (Centre L´ eon B´ erard). Clinical assessment and blood parameters were recorded. Candidate prognostic factors for overall survival (OS) with a 0.05 significance level in univariate analysis were entered in a multivariate Cox model. Results: Median age was 58.5y (range: 37 76). 62 percent of the pts were PS = 0 or 1. After inclusion pts received second-line (22.5%), third-line (5%) chemotherapy. Median follow-up and median OS were 12 months and 6 months respectively. In univariate analysis, factors associated with short OS were PS > 2, weight loss >10% and abnormal blood parameters: hemoglobin (Hb), platelet counts and IL6. The self-assessment by pts of the quality of life was not significantly correlated with OS. Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for short OS. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively.