Factors In Lung Cancer Patients Research Articles

Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer

Liver metastasis is one of the most important prognostic factors in lung cancer patients. However, current therapies are not sufficient. RNA interference provides us a powerful and promising approach for treating human diseases including cancers. Herein, we investigated the in vitro effects of PLK-1 small interfering RNA (siRNA) on human lung cancer cell lines and the in vivo usage of PLK-1 siRNA with atelocollagen as a drug delivery system in a murine liver metastasis model of lung cancer. PLK-1 was overexpressed in cell lines and in cancerous tissues from lung cancer patients. PLK-1 siRNA treatment inhibited growth and induced apoptosis in a concentration-dependent manner. To verify in vivo efficacy, we confirmed that atelocollagen was a useful drug delivery system in our model of implanted luciferase-labeled A549LUC cells by detecting reduced bioluminescence after an i.v. injection of luciferase GL3 siRNA/atelocollagen. PLK-1 siRNA/atelocollagen was also successfully transfected into cells and inhibited the progression of metastases. This study shows the efficacy of i.v. administration of PLK-1 siRNA/atelocollagen for liver metastases of lung cancer. We believe siRNA therapy will be a powerful and promising strategy against advanced lung cancer.

Significance of the urinary 8-OHdG level as an oxidative stress marker in lung cancer patients

In the present study, we investigated the relationship between the urinary excretion rate of the oxidized nucleoside 8-hydroxydeoxyguanosine (8-OHdG) and clinical factors in lung cancer patients. The present study included 100 patients, who underwent a lung surgery. The patients included 62 men and 38 women with a mean age of 65.5 years ranging from 35 to 82. The diagnosis included 81 primary lung cancers, 9 metastatic lung cancers and 10 benign lung diseases. Urine samples collected for 24h were analyzed for the content of 8-OHdG using an ELISA assay. The urinary excretion rate of 8-OHdG in smokers was significantly higher than that in never-smokers. Specifically, the 8-OHdG excretion rate of current smokers was higher than that of patients who had quit smoking for longer than 1 month. Excluding current smokers, the urinary excretion rate of 8-OHdG did not relate to age or gender, but to the malignant potential of the disease. The urinary 8-OHdG level increased in the order of metastatic lung cancer, primary lung cancer and benign disease. In lung cancer patients, furthermore, the mean urinary 8-OHdG level of patients with stages II-IV disease was significantly lower than that of patients with stage I disease. Smoking significantly increased the urinary excretion rate of 8-OHdG, suggesting that smoking causes an increased rate of oxidative DNA modifications. On the other hand, the capacity to repair oxidative DNA modifications might be impaired to some extent in cancer patients.

Circulating tumor cells (CTC) as a prognostic and predictive factor in Lung Cancer Patients–a pilot study in PUMCH

22201 Background: We explored the clinical value of circulating tumor cells (CTCs) in prognosis and the assessment of treatment effects for patients with lung cancer. Methods: In a prospective, sin...

Prognostic factors for lung cancer patients with brain metastases treated with whole brain radiotherapy

7570 Background: The purpose of this retrospective study was to clarify the role of whole brain radiotherapy (WBRT) in lung cancer patients with brain metastases (BM). Methods: Between February 1998 and October 2005, 103 consecutive lung cancer patients received WBRT for BM. The patients included 77 men and 26 women, ranging in age from 34 to 84 years with a median age of 65 years. Thirty-six of the patients had SCLC and 67 had NSCLC. Fifty-two patients had an ECOG performance status (PS) score of 0 to 2, and 51 had a PS score of 3 or 4. Seventy-nine patients (77%) had symptomatic BM, and 72 had multiple BM (70%). The mean dose of brain radiation was 38±8.3 Gy. Following radiation treatment, the median survival time (MST) for all patients was 4.0 months, and the 1-year survival rate was 14%. Multivariate analysis was performed using Cox proportional hazards model to evaluate the following: sex, age (<60 years vs. ≥60 years), histology (SCLC vs. NSCLC), PS score (0–2 vs. 3–4), number of BM (single vs. mult...

Demographic and geographic features as prognostic factors in lung cancer patients

Demographic and geographic features as prognostic factors in lung cancer patients

Analysis of prognostic factors in 352 lung cancer patients with brain metastases.

Lung cancer has become one of the most common malignant tumors in China. The prognosis of lung cancer is poor mainly because of relapse and distant metastases and brain metastasis occurs frequently. This study attempts to evaluate the prognostic factors in lung cancer patients with brain metastases. The information in the study may be useful for the clinicians to make some decisions. The clinical data of 352 lung cancer patients with brain metastases in our hospital from the year of 1997 to 2005 were retrospectively reviewed. The multivariate analysis was performed with Cox's proportion risk model. Survival analysis was compared with Kaplan-Meier method and log-rank test was used respectively. Statistical significance was defined as P<0.05. The univariate analysis showed that patients' performance status (PS score), age, the number of brain metastases, the absence or presence of extracranial metastases and metastatic symptoms, multimodality treatments were related to survival period(P<0.05). The multivariate analysis indicated that patients' performance status (PS score), age and the number of brain metastases were closely related to their prognosis (P<0.05). Performance status(PS score), age and the number of brain metastases are the independent prognostic factors in lung cancer with brain metastases. The patients with PS score 0-1, age<=60 years and single brain metastasis have longer survival and they can benefit from treatments.

Overcoming a stigma: the lung cancer patient in the intensive care unit

Before embarking on a discussion of the lung cancer patient in intensive care, it is important to clarify that this editorial will not be referring to the group of patients with a good prognosis having undergone surgery with a curative intent, but to patients whose malignancies more or less determine the outcome in terms of survival time, and who are suffering from acute or subacute deterioration in the form of a complication resulting either from the underlying disease or tumour or from treatment-related sequelae. In such cases, most doctors' knowledge and experience will be confounded with those dark emotions that serve to sustain a misconception that is still associated with lung cancer patients, despite certain advances in treatment achieved through multimodal regimes and “new drugs”. As the technical possibilities of intensive medicine, including in particular the improvement of ventilation techniques with varying degrees of invasiveness, increase, it seems desirable to take a fresh look at the survival and prognostic factors in lung cancer patients admitted to a medical intensive care unit (ICU). Adam and Soubani 1 have taken up this challenge. Their results are reported in the present issue of the European Respiratory Journal . At first sight, the range of reasons leading to referral for intensive care appears quite familiar and unspectacular: first, pneumonia, followed by exacerbated chronic obstructive pulmonary disease, pulmonary oedema and haemoptysis. As with most studies of this kind 2, 3, the analysis is retrospective. However, that does not, by any means, detract from its evidential value, since the criteria on which referrals of critically ill patients with nonmalignant disease to intensive care have been based to date fail to do justice to lung cancer patients with their complex requirements 4, 5. As in other recent studies published in the field 2 …

Outcome and prognostic factors of lung cancer patients admitted to the medical intensive care unit

The aim of the present study was to assess the outcome of lung cancer patients who were admitted to a medical intensive care unit (MICU) and to identify the measurable predictors of their MICU outcome. The retrospective study took place at the MICUs of a university-affiliated medical centre and involved adult lung cancer patients admitted to the MICU between January 1998 and October 2005. A total of 139 lung cancer patients were included during the study period. The mean age+/-sd at MICU admission was 64.2+/-10.2 yrs (48% males, 52% females). In total, 96 (69%) patients had nonsmall cell lung cancer, 18 (13%) patients had small cell lung cancer, and one patient had mesothelioma. The MICU mortality was 22% (31 patients), while the in-hospital mortality was 40% (56 patients). Sixty-eight (49%) patients required mechanical ventilation (MV), with MICU mortality of 38% and in-hospital mortality of 53%. The independent predictors of poor MICU outcome were: the need for MV; Acute Physiology And Chronic Health Evaluation III and Simplified Acute Physiology Score III scores; the use of vasopressors; positive blood cultures; high serum lactate; two or more organ system failures; and the need for adult cardiac life support. On multivariate analysis, only the need for vasopressors and the presence of two or more organ system failures predicted poor MICU outcome. The present study shows that the medical intensive care unit outcome of lung cancer patients is better than previously reported. Intensive care and mechanical ventilation should not be considered futile care in this patient population. While there were no absolute predictors of mortality, the need for vasopressors and the presence of two or more organ system failures predicted poor medical intensive care unit care.

Elevated pleural fluid RCAS1 is a diagnostic marker and outcome predictor in lung cancer patients

RCAS1, a type II membrane protein also secreted in soluble form, may be important in tumor cell evasion of immune surveillance and contribute to the aggressiveness of human tumors. We examined the implications of elevated pleural fluid RCAS1 at the onset of effusion in lung cancer patients. Of 102 patients presenting with pleural effusion, 59 proved to have a malignant effusion and 43, nonmalignant. Malignant effusions exhibited higher RCAS1 concentrations than nonmalignant effusions (mean +/- SD; 36.3 +/- 114 vs. 2.7 +/- 1.8 U/ml; p=0.014). Lung cancer patients with pleural fluid RCAS1 concentrations below 15 U/ml had a longer mean survival than those with higher concentrations (4.7 vs. 1.7 months; p<0.05). By multivariate analysis, pleural fluid RCAS1 was an independent prognostic factor in lung cancer patients with effusion. In conclusion, RCAS1 determination at onset of pleural effusion is informative for both diagnosis and outcome prediction in lung cancer patients.

TH‐C‐224C‐05: Analysis of Radiation‐Induced Pneumonitis in Lung Cancer Patients

Purpose: To study clinical, physiological, biological and dose‐volume factors in lung cancer patients who developed symptomatic radiation‐ induced pneumonitis (RP). Method and Materials: Data from two‐hundred patients with non‐small cell lung cancer who received 3D conformal radiotherapy (RT) treatment were analyzed using an in‐house developed MATLAB‐based analysis tool, EUCLID. The effect of 52 clinical, physiological and biological factors, as well as dosimetric variables extracted from the lung dose‐volume histogram (DVH) was analyzed using univariate and multivariate approaches. Results: Thirty nine patients (19%) developed RP. In the univariate analysis, the forced expiratory volume in 1 second (FEV1) post‐treatment, normal tissue complication probability (NTCP), mean lung dose, history of smoking, level of TGF‐β post‐treatment and nodal stage were associated with RP (p‐range 0.001–0.033). When considering the percentage of volume of lung receiving more than a specified dose, we found that 60 Gy (V60) yields the strongest correlation with RP (p=0.0001). In the multivariate analysis, a logistic regression analysis was performed using different sets of uncorrelated variables. The predictive power of the model was quantified using the area under the Receiver‐Operating Characteristic (ROC) curve. The best result was obtained with V30, FEV1, age, time of chemotherapy (before, after or concurrent with RT) and Lobe (location of tumor inside the lung). The area under the curve for these variables was 0.85. While only the regression coefficients of V30 and FEV 1 determined a correlation with RP with a p‐value less than 0.05, the exclusion of the other three variables led to a lower area under the curve. Conclusion: V30 and FEV 1 were the best predictors of symptomatic RP after external beam RT for lung cancer. Multivariate analysis showed that other clinical factors that are not individually strongly associated with RT can be included in a regression model to increase the predictive power of that model.

The Lung Cancer Database Project at the National Cancer Center, Japan: Study Design, Corresponding Rate and Profiles of Cohort

The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.

Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer

BackgroundMedical oncologists continue to use performance status as a proxy for quality of life (QOL) measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy.MethodsWe enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2).ResultsPatient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival.ConclusionLCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.

Tissue MMP-2/TIMP-2-complex are better prognostic factors than serum MMP-2, MMP-9 or TIMP-1 in Stage I–III lung carcinoma

Matrix metalloproteinases (MMPs) are involved in tumor growth and spreading. Here, we investigated the tumor immunoreactive protein of MMP-2, MMP-9 and TIMP-1 as well as the levels of circulating total TIMP-1 and MMP-2/TIMP-2-complex as prognostic factors in lung cancer patients. The material included 59 patients, 30 with a squamous cell carcinoma, 21 with an adenocarcinoma and eight with other histology. Circulating antigens were measured by ELISA assay and the protein expression in primary tumors was analyzed by streptavidin–biotin immunohistochemical staining using specific monoclonal antibodies. The strong positivity for MMP-2 or MMP-9 in tumor predicted poor prognosis. The 5-year survival rates were 83 or 85% in patients negative for MMP-2 or MMP-9, respectively. Only 17% of the patients with a tumor highly positive for MMP-2 and 43% of those with a high positivity for MMP-9 survived at that time (Cox regression P=0.042 for MMP-2 and log rank P=0.046 for MMP-9). On the contrary, strong tissue positivity for TIMP-1 demonstrated a tendency for a favorable survival, although the difference did not reach statistical significance. In patients with a squamous cell carcinoma Stage I, low serum TIMP-1 (≤300 ng/ml) also predicted unfavorable survival (log rank P=0.033). Further in subgroup of patients treated by lobectomy ( n=29), the high levels of circulating MMP-2/TIMP-2-complex (≥300 ng/ml) associated with an increased survival rate, the 5-year survival being 81 versus 34% (log rank P=0.069) in patients with high or low serum levels for MMP-2/TIMP-2-complex, respectively. Tissue MMP-2 correlated to high expression of MMP-9 immunoreactive protein ( P=0.003), but the serum levels of MMP-2/TIMP-2-complex or TIMP-1 did not correlate to the immunostaining of the corresponding tumors. We conclude that in lung carcinoma the best prognostic value is achieved by using immunohistochemistry for MMP-2 and MMP-9. In early disease, however, serum TIMP-1 or MMP-2/TIMP-2-complex could offer some further prognostic value.

Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs)

The expression of vascular endothelial growth factors (VEGFs) in tumors including lung cancer is considered to be associated with tumor development via capillary and lymph vessel neogenesis. Dissemination of the tumor cells to the pleura or regional lymph nodes is a critical poor prognostic factor for lung cancer patients. To investigate how VEGFs expressed in the intrathoracic infiltrating lung cancer cells participate in disease progression, we established stably VEGF-A-, VEGF-C-, VEGF-D-, VEGF-A and VEGF-C-, and VEGF-A and VEGF-D-expressing large cell lung cancer clones (TKB5/VEGF-A, TKB5/VEGF-C, TKB5/VEGF-D, TKB5/VEGF-A/C, and TKB5/VEGF-A/D), orthotopically inoculated these into the right thoracic cavity (i.t.) of nude mice, and evaluated the subsequent development of lung lesion, pleural effusion, pleural dissemination, and lymph node metastasis. While there were no significant differences either in culture or in subcutaneous tumor cell growth between the empty vector-transfected group (TKB5/empty) and each transfectant, the i.t. model demonstrated significantly different biological properties between the transfectants. TKB5/empty-inoculated mice frequently developed a large tumor on the pleura without pleural effusion, dissemination, or lymph node (LN) metastasis. In contrast, VEGF-A promoted a bloody pleural effusion (6/14), and VEGF-A and VEGF-D frequently generated pleural dissemination (11/14 and 9/11, respectively). Although both VEGF-C and VEGF-D generated LN metastasis (6/10 and 8/11, respectively), the locations of the metastasized LNs were quite different. TKB5/VEGF-C metastasized on the same side of axillary LNs as i.t. (right axillary LNs), whereas TKB5/VEGF-D metastasized to the mediastinal and left axillary and/or cervical LNs. Since the TKB5/VEGF-A/C or TKB5/VEGF-A/D co-transfectants revealed overlapping tumor progression patterns of VEGF-A and VEGF-C or VEGF-D, the metastatic LNs had abundant new capillaries and were larger than those of TKB5/VEGF-C or TKB5/VEGF-D-inoculated mice. Our results clearly demonstrate that VEGF-A secreted from intrathoracic lung cancer cells plays important roles in producing pleural effusion, dissemination, and capillary neogenesis, that VEGF-C is involved in LN metastasis, and VEGF-D in pleural dissemination and LN metastasis. It is most likely, however, that the mechanisms by which VEGF-C promotes LN metastasis are different from those of VEGF-D. The regulation of the expression of VEGFs in intrathoracic lung cancer cells might be a useful therapeutic approach to inhibiting tumor development and improving patient prognosis.

Traditional Chinese medicine Astragalus reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients

Th2 cytokine is predominant in tumor patients and was found to be associated with tumor progression. Reversing of Th2 dominant status is thought to be a promising strategy. In the present study, peripheral blood mononuclear cells (PBMNC) of 37 lung cancer patients and 19 healthy subjects were prepared and used for examination of cytokine secretion and gene expression. The positive percentage of mRNA transcripts of Th1 cytokines (8.1% for IFNgamma and 13.5% for IL-2) in patients' PBMNC were lower than those of Th2 cytokines (70.3% for IL-4, 64.9% for IL-6 and 83.8% for IL-10). The gene expression capacity (measured as relative intensity to ratio of beta-actin) of patients for Th1 cytokines was low, but constitutively relatively high for Th2 cytokines. Both positive percentage and relative intensity were lower in transcript factor for Th1 cytokine, T-bet (40.5% and 0.139, respectively) than those for Th2 cytokine, GATA3 (89.2% and 0.364, respectively). Traditional Chinese medicine, Astragalus (AG) was observed to reverse Th2 status of lung cancer. AG enhanced culture supernatant and gene expression levels of Th1 cytokine (IFNgamma and IL-2) and its transcript factor (T-bet), and reduced those of Th2 cytokines in cultured PBMNC of lung cancer patients. These results demonstrated that traditional Chinese medicine AG might reverse the Th2 predominant status in lung cancer patients, which is a probable alternative therapeutic regime in future.

P-371 Therapeutic compliance and its related factors in lung cancer patients

P-371 Therapeutic compliance and its related factors in lung cancer patients

P-105 Incidence and prognostic factors in lung cancer patients with coincident HIV infection

P-105 Incidence and prognostic factors in lung cancer patients with coincident HIV infection

Impact of limited pulmonary function on the management of resectable lung cancer

Aims: Limited pulmonary function (LPF) related to obstructive disease and emphysema or due to significant lung toxicity resulting from chemotherapy regimens are frequent co-morbidity factors in lung cancer patients. Purpose of this study was to investigate the frequency of LPF in lung cancer and its impact of on surgical eligibility and postoperative outcome. Materials and methods: We analyzed a series of 255 consecutive patients with otherwise resectable lung cancer, admitted to our department between January 1998 and December 1999. Patients were considered affected by LPF if their forced expiratory volume in one second (FEV1%) and/or diffusing lung capacity for carbon monoxide (DLCO%) was less than 50% of predicted normal values. Perioperative mortality, major and minor complications were analysed according to lung function status. Results: A total of 42 (16.5%) patients presented with significant limitations of the pulmonary function (LPF). Of these, 11 (26%) cases were excluded from surgery because of the severity of pulmonary disease. In the group of 244 patients who underwent surgery, the 31 LPF cases showed a slightly higher frequency of preoperative induction therapies (42 vs. 30%) and sublobar resections (33 vs. 8%) in comparison with the other 213 resected cases. However, no difference was observed in median hospital stay (7 days in both groups), major morbidity (13 vs. 11%) or mortality (0 vs. 1.4%). Conclusions: A strict and careful selection of patients, guided by concurrent analysis of different functional tests, allowed to offer surgery with a very low complication rate to the majority of patients with limited pulmonary function. A volume reduction effect was evident in selected patients with severe emphysema.

Expression of Matrix Metalloproteinases-9 and Stromelysin-3 in Peripheral Blood in Patients with Lung Cancer

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

The Value of Serum for Diagnosis and Evalucation of Disease Extent in Lung Cancer Patients

Objective To find out the relationship of serum interlcukin\|6 for diagnosis and evalucation of disease extent in patients with lung cancer.Methods serum IL\|6 were detected in 44 cases of lung cancer patients and 34 cases normal subject using radio Immunoassay(RIA).Results T test dicated serum concentration of IL\|6 had significent statistical differences among twl groups (P0.01) .But the level of IL\|6 had not statistical differences in lung cancer patients of different tumor tissue.The serum IL\|6 in the patients with metastasis(stage M\-1) were significantly lower than in those with stage of M\-0 (P0.05) .Conclusion The study indicates that serum IL\|6 may act as diagnosis and prognosis factor for lung cancer patients.