【Abstract】 Background and objective As there is a sharp increase in the incidence oflungcancerin women in re- cent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and beter prognosis. he aim of this study is to analyze the clinical data of women withadvancednon-smallcelllungcancer (NSCLC) retrospectively to explore the prognosticfactors. Methods Clinical data of541femalepatientswithadvanced NSCLC were collected and fol- lowed up till death. he primary endpoint is overall survival (OS). SPSS 11.0 statistical analysis sotware was used for univariate and multivariate analysis. Results he mean age is 59 years (20 years-86 years), adenocarcinoma account for 80.2% (434/541). he median OS was 15 months (95%CI: 13.87-16.13), and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respective- ly. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the irst-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were signiicantly correlated with the OS and survival rate (P<0.05). Combined with multivariate anal- ysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to irst-line chemotherapy were independent prognostic factor for survival (P<0.05). Conclusion here is a higher percentage of adenocarcinoma in fe- male NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to irst-line chemotherapy may become independent prognosticfactors for survival offemalepatientswithadvanced NSCLC.
Our results demonstrate that a quantitative determination of plasma mSHOX2 DNA ap- pears to be useful for the monitoring of a treatment response for advanced stage lungcancerpatients. The turn-over rate ofcell-free DNA is rather high as the half-life of extracellular nu- cleic acids was determined to be less than six hours in an animal model . This correlates well with our observation of a fast and strong decline of plasma mSHOX2 DNA inpatients re- sponding to the therapy which holds true for the monitoring of NSCLC and SCLC patients alike. An additional advantage of this method is its applicability for patientswith a very low pre-therapeutic mSHOX2 value. We demonstrated that a mSHOX2 measurement taken one week after the start of a therapy is able to divide between responders and non-responders with a very high specificity. If this result can be verified in a large study, physicians have the possibil- ity to switch therapies or spare patients from an invalid therapy. Additionally, we used the data from all 36 patients, i.e. including the patientswith a mSHOX2 baseline value of zero and the second-line patients for a Kaplan-Meier survival curve analysis. Interestingly, we demonstrated that the patientswith a baseline plasma mSHOX2 level below the median had a slightly longer survival time. When this analysis was performed at blood draw one after therapy start this dif- ference between patients responding to the therapy and non-responders was statistically signif- icant with a p 0.001. The question whether patientswith a very low mSHOX2 baseline value behave differently from patientswith a high(er) mSHOX2 level and whether it might be possi- ble to define a pre-therapeutic cut-off value which has a predictive meaning has to be answered in a large study which will be conducted in a multicentric approach.
Correlate the inhibitor of gefitinib this inhibitor for signaling to increase grows. The patients who are affected by gefitinib are exposed to screening for identification oflungcancer . Production oflungcancer for a patient is better against prognosticfactors and NSCL stages across the year. These probability of detection for lungcancer from ACOSOG Z0030 and CALGB 9761 is 72% and 79%.A subgroup of patient with disease at 1A Stage were at high risk and these may be treated by chemotherapyThe patient who were better than positron Emission Tomography for wide range of cancers PET will play valuable role for RT planning. In RT planning the physician should be aware when request is for PET scan  Non- smallcell lungcancer theFDG-
Interstitial lung disease (ILD) is considered as a major safety concern for EGFR-TKIs. The incidence of ILD among gefitinib-treated patients was 0.44–2.0%, and the mortality rate of ILD was reported to be 0.12–0.5%.[19–21] ILD was also found inpatients receiving erlotinib, with the incidence of 0.1–4.8% and the mortality of 0.8–2.4%.[22–26] Several factors were reported to contribute to the development of ILD, including older age, poorer performance status, smoking status, shorter duration since diagnosis of NSCLC, reduced normal lung, preexisting ILD, and concurrent cardiac disease. For icotinib, one ILD case was reported in a phase I study, and no ILDs was reported with icotinib or gefitinib in the ICOGEN study. In the IV phase study, three ILD-like events were observed, and all of these cases were in elderly patientswith stage IV adenocarcinoma who had received at least one platinum-based chemo- therapy. In the present study, one ILD case was reported who had received two platinum- based chemotherapy regimens. Investigators considered this ILD as icotinib-related by CT scan and clinical syndrome.
Methods: Seventy eight consecutive patientswithadvanced NSCLC treated in Department of Chemotherapy, UMHAT- Dr. G. Stranski, Medical University- Pleven between 2006- 2008 were retrospectively analyzed. Of those, 27 patients /34, 6%/ had low hemoglobin /HB/ level (<120g/L for men and <110g/L for women) prior to start chemotherapy. The HB levels were obtained at the time of their first visit to the hospital. All patients received chemotherapy regimen consists of intravenous administration of Gemcitabine 1250 mg/m2 day 1 and 8 and cis- Platinum 80mg/m2 day 1 with repetition over 21 days. Survival analysis was evaluated by Kaplan- Meier test.
Exosomes are nano-sized vesicles of endolysosomal origin, released by several cytotypes in physiological and pathological conditions. Tumor derived exosomes, interacting with other cells of the tumor microenvironment, modulate tumor progression, angiogenic switch, metastasis, and immune escape. Recently, extracellular vesicles were proposed as excellent biomarkers for disease monitoring and prognosis incancerpatients. Non-smallcelllungcancer (NSCLC) has a poor 5-year survival rate due to the delay in the detection of the disease. The majority ofpatients are diagnosed in an advanced disease stage. Exosomes might be promising beneficial tools as biomarker candidates in the scenario of NSCLC, since they contain both, proteins and miRNAs. The clinical case reported in this manuscript is a proof of concept revealing that NSCLC exosomes and sorted miRNAs might constitute, in a near future, novel biomarkers. This review summarizes the role of exosomes in NSCLC, focusing on the importance of exosomal microRNAs inlungcancer diagnosis and prognosis.
In order to better characterize intratumoral heterogeneity of EGFR, we microdissected bulk tumor tissue to obtain 28–34 foci per tumor and analyzed each focus for EGFR mutation status using qualitative and semi-quantitative methods. Most of the microdissection foci were identified as EGFR mutant-type with EGFR mutation contents ranging from 1% to 100%. Theoretical and experimental studies have reported that cancer cells of the same genotype locate contiguously . Analysisof a small sample excised from tumor tissue would likely indicate a genetically identical population ofcancer cells. However, our analysisof EGFR mutation statuses from numerous intratumoral foci in- dicated heterogeneity. We excluded non-malignant sites by microscopic visualization, and every microsampled specimen was cross-checked to confirm that the percentage of tumor tissue was at least 90%, ensuring that microdissected areas were not contam- inated by non-cancerous cells. Thus, our data confirmed the existence of intratumoral EGFR mutational heterogeneity.
Data from the phase III trials were evaluated through linear regression analysis, by assigning a weight equal to the sample size to each trial. The strength of associations was defined a priori using the commonly accepted criteria for the coefficient of determina- tion (r 2 ); briefly, it gives the proportion of the variance of one variable that is predictable from the other variable. It is a measure that allows for the determination of how certain one can be in making predictions from a certain model. The coefficient of determination is such that 0#r 2 #1, and a higher r 2 score indicates a stronger association. Correlations were described graphically through bubble plots in which each bubble represents a pair of arms with size proportional to the sample size of each trial. To examine possible differential associations between MST and MPFS and between MST and SPP, the analysis was repeatedly conducted after stratifying several clinical factors (Table 4). Differential associations were then evaluated by entering multipli- cative interaction terms between each factor.
prognosis among patientswith completely resected NSCLC but that arterial invasion did not . However, in most of the studies, arterial and venous invasion has not been separately studied pathologically due to the inability in some cases to discriminate between arterial and venous invasion. In addition, most of the studies included in this meta-analysis investigated the correlation between intratumoral BVI and prognosis, but some studies demonstrated the prognostic role of extratumoral vascular invasion. Shimada et al. reported that both intratumoral and extratumoral vascular invasion were significant prognosticfactors, but only the extratumoral vascular invasion group was associated withadvanced pathologic staging, lymph node metastasis, and lymphatic permeation . Our meta-analysis focused on the effect of tumor vascular invasion on the survival of NSCLC patients irrespective of whether these studies detected intratumoral or extratumoral vascular invasion or whether they determined arterial and venous invasion. Although almost all intratumoral blood vessels are occluded by the surrounding tumor cells and stromal cells, intratumoral and extratumoral blood vessels are thought to be functional blood vessels. In fact, Shimada et al., found that all extratumoral vascular invasion cases also had intratumoral vascular invasion .
Recently study revealed that CEA level change during EGFR-TKIs therapy can be used to a predictor of survival. However, LMR change (MBR) during EGFR-TKIs was seldom men- tioned before. Our study revealed patientswith higher MBR had better PFS (11.5 vs 5.7 months, p < 0.001). Although patientswith high MBR had almost twice longer OS than those with low MBR (22.1 vs. 12.9 months), no significant was noted in log-rank test. (p = 0.074) It needs more studies to prove if lack of significance in MBR on OS were due to small study popu- lation or a true negative result.
Subgroup analysis is a method for exploring the sources of heterogeneity and for increasing the reliability of an article. Tumor stage is an important factor that affects the prognosis of NSCLC . While the patientsin the included studies were of different disease stages, Zhu et al. studied only stage IB NSCLC patients , and Li et al. did not report the disease stage of the pa- tients they enrolled . Therefore, we performed subgroup analysis according to stage, and found that TIMP-2 expression was a statistically significant favorable factor inpatientswith stage I-IV NSCLC. From this, we may assume that high TIMP-2 expression is not only related to out- come in early-stage NSCLC, but also the late stages. The methods used to measure TIMP-2 ex- pression varied between the studies, which may have reduced the reliability of our result. We selected the most commonly applied method, i.e., IHC, for the subgroup analysis and found that the conclusion that high TIMP-2 expression is associated with good prognosis in NSCLC re- mained the same if only IHC was used to assess TIMP-2 expression levels. The percentage of high TIMP-2 expression ofpatientsin the included studies ranged 31–67.3%. The reasons for this may be the differing states of illness, definitions of positive expression, and race or sex com- position of the sampled populations in the included studies. Therefore, we selected studies where the percentage of high TIMP-2 expression was <50% for subgroup analysis to determine the strength of the previous conclusion. This subgroup analysis also suggested that high TIMP-2 ex- pression in NSCLC patients was a significant predictor of good survival. Thus, we believe that TIMP-2 may be a relatively stable indicator of favorable prognosis in NSCLC.
TERT is of great importance incancer initiation and progression. Many studies have demon- strated the TERT polymorphisms as risk factors for many cancer types, including lung can- cer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT poly- morphisms with clinical outcome ofadvancednon-smallcelllungcancer (NSCLC) patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS), overall survival (OS), and grade 3 or 4 toxicity. Seven poly- morphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC pa- tients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype) to 56.4% (C/A genotype; ad- justed OR, 3.58; P=1.40×10 -4 ). It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023). In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild- type genotypes (P=0.002). The results from the current study, for the first time to our knowl- edge, provide suggestive evidence of an effect of TERT polymorphisms on disease progres- sion variability among Chinese patientswith platinum-treated advanced NSCLC.
AKT has been found to play a role in the survival ofcancer cells in breast, prostate, ovary, and brain tissue [25-28]. It was also identified as a constitutively active kinase that promotes survival of NSCLC cell . Recently, a clinical study of p-AKT expression in tissue from patientswith bronchial epithelial dysplasia and malignancy corroborates this hypothesis. They observed strong p-AKT staining in 12 of 44 normal bronchial biopsy specimens, 4 of 9 reactive specimens, 22 of 25 dysplastic specimens, and 25 of 76 NSCLC specimens. Tsao et al.  considered that AKT activation may be more strongly associated with the early stages of malignant transformation than with progression to frank neoplasia .
Lungcancer remains the most common cause of can- cer death worldwide for both men and women. NSCLC constitutes about 75%- 85% of all lungcancer cases . Despite recent improvements of diagnostic technologies, approximately 50% ofpatients diagnosed with NSCLC present at diagnosis withadvanced (stage III or IV) disease. The prognosis and overall survival (OS) in these patients still remain poor because local and distant failures are com- mon . Although can be curative at the early stages of NSCLC, the majority ofpatientswithadvanced stage NSCLC is not amenable to curative resection at diagnosis . The median survival time for patientswith untreated advanced or metastatic NSCLC is only 4- 5 months, with a survival rate at one year of only 10% . The treatment options for these patients are limited although platinum- based chemotherapy has been shown to provide survival
As for systemic inflammation, cancer can induce local or systemic inflammation, which is mediated by activation of transcription factors and production of major inflammatory cyto- kines . On the other hand, cancer-related inflammation can influence cell proliferation, cell survival, angiogenesis, tumor cell migration, invasion and metastasis of adaptive immunity . Admittedly, neutrophil which is the most common and indispensable component of inflammation plays very important role in inflammatory tumor microenvironment . Some studies have revealed derangement in the full blood count such as neutrophilia, was known poor independent prognostic factor for many solid tumors [13–15]. In addition, CRP which is the most widely accepted proxy for systemic inflammation was also identified as a prognostic factor in both advanced and resectable NSCLC [16, 17]. However, CRP is not commonly used in clinic because of low sensitivity and unconventional detection. Nutritional status ofcancerpatients, commonly reflected by serum albumin, is also a determinant of survival in many kinds ofcancer. Hypoalbuminemia, an objective parameter of malnutrition , has been reported as a negative prognostic factor for survival inadvanced NSCLC , and other malig- nancies [20, 21]. Nevertheless, the predictive efficiency of combination of pretreatment albu- min level which reflects nutritional status and pretreatment neutrophil level which reflects systemic inflammation has not been reported before.
ABSTRACT: Introduction: Outcomes data on Non-SmallCellLungCancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival ofpatientswith NSCLC in a Brazilian private oncologic institution. Methods: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. Results: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed inadvanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 – 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 – 14.4). Conclusions: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages. Keywords: Lung neoplasms. Epidemiology. Supplemental health. Neoplasm staging. Survival analysis. Treatment.
Objective: Lungcancer is a global public health problem and is associated with high mortality. Lungcancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time ofpatientswithnon-smallcelllungcancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. Methods: This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-speciic survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. Results: The estimated 60-month speciic- disease lethality rate was 86.0%. The 60-month disease-speciic survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognosticfactors identiied in the study population. Conclusions: In this cohort ofpatients, the disease-speciic survival probabilities were extremely low. We identiied no factors that could be modiied after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences oflungcancer.
Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in pa- tients over 70 years of age withadvanced NSCLC. We allowed inclusion of RCTs speciically designed for the elderly population and those de- signed for elderly subgroup analyses.
is that, when the method is more sophisticated, the number ofpatientswith occult metastases in the regional lymph nodes is higher. Consequently, the simultaneous use of more than one technique can increase the detection of positive lymph nodes considerably. Therefore, until we discover the true importance of isolated malignant cells or microme- tastases in regional lymph nodes, it is fundamental that new techniques be developed in order to improve detection. Only with larger samples, similar histopathological criteria, and analyses of possible associations regarding prognosis will we be able to discern the true importance of these findings. This should occur in the near future.
However, our study has several limitations, as we could not prevent all potential bias among these studies. Although 21 studies were included in the final analysis, the average sample size was small (mean,98). For articles without HR and 95%CI, we contacted the corresponding author, but received no reply. Consequently, we extrapolated these metrics from the data or curves in these articles indirectly, which could be another potential source of bias. Different methods of examining bFGF expression, primary antibody source and concentration, and threshold cut-off values may introduce more bias as well. IHC is a relatively complicated tech- nique with many steps and is observer-dependent. Moreover, our meta-analysis data did not include information on age, smoking status, tumor size and other factors, which might result in confounding bias. Lastly, we included studies which dichotomized bFGF expression into the high and low expression group. Other studies that included bFGF expression as a continuous variable were excluded because the data was not extractable.