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Abstract: Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Firstly, pemetrexed was approved in combination with cisplatin for the treatment of malignant pleural mesothelioma. Successively, it has been studied, as single-agent, in phase II and III trials for second-line therapy of non-small cell lung cancer (NSCLC). Based on these results, pemetrexed has been registered for the treatment of recurrent NSCLC. The next step was to test pemetrexed plus cisplatin versus gemcitabine plus cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non-inferiority, randomized trial. This trial reported the pemetrexed plus cisplatin regimen to be not inferior, in terms of activity and efficacy, to the control arm but statistically better tolerated. The role of pemetrexed as maintenance therapy after first-line therapy for advanced NSCLC is currently being evaluated into a phase III trial. The consistency of the results of these recent studies has identified a predictive effect of NSCLC non-squamous histology for pemetrexed. To date, pemetrexed is registered, at the dose of 500mg/m2 on day 1 of a 3-week schedule, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with non-squamous NSCLC.This review shows the latest and indicates the future developments of pemetrexed in the treatment of advanced NSCLC patients.

Abstract: Background and purpose: Patients with malignant pleural mesothelioma (MPM), who undergo chest instrumentation, may develop seeding at the site of intervention, leading to subcutaneous tumour. This is believed to be reduced by the common practice of prophylactic irradiation to intervention tracts (PIT). However, evidence to support PIT is currently inadequate and contentious.Materials and methods: We carried out a systematic search of published literature for articles relating to the incidence of chest wall intervention tract metastases and the use of PIT in mesothelioma. In addition, a survey of current practice was conducted in 54 UK oncology centres.Results: Fourteen studies revealed an incidence of chest wall intervention tract metastases of 0â??48% with a trend toward a higher rate of metastases for more invasive procedures. Three randomised controlled trials (RCTs), two prospective non-randomised studies and five retrospective series met the eligibility criteria to evaluate the role of PIT in MPM. Of the three RCTs, two did not support the use of PIT. None of the RCTs included patients who had received systemic chemotherapy. Of the oncology centres responding to the survey, 75% practiced PIT, and 80% would be interested in a trial to determine the efficacy of PIT.Conclusions: No consensus has been reached to support the use of PIT. However, most centres in the UK still offer PIT. There was widespread interest in a randomised controlled trial to establish PIT efficacy in the era of effective systemic chemotherapy for malignant pleural mesothelioma.

Abstract: Telomeres are responsible for the protection of the chromosome ends and shortened telomere length has been associated with risk of multiple cancers. Genetic variation in telomere-related genes may alter cancer risk associated with telomere length. Using lung cancer cases (n=120) and population-based controls (n=110) from Xuanwei, China, we analyzed telomere length separately and in conjunction with single nucleotide polymorphisms in the telomere maintenance genes POT1, TERT, and TERF2, which we have previously reported were associated with risk of lung cancer in this study. POT1 rs10244817, TERT rs2075786, and TERF2 rs251796 were significantly associated with lung cancer (ptrendâ?¤0.05). The shortest tertile of telomere length was not significantly associated with risk of lung cancer (OR=1.58; 95% CI=0.79â??3.18) when compared to the longest tertile of telomere length. When stratified by genotype, there was a suggestion of a doseâ??response relationship between tertiles of telomere length and risk of lung cancer among the POT1 rs10244817 common variant carriers (OR (95% CI)=1.33 (0.47â??3.75), 3.30 (1.14â??9.56), respectively) but not among variant genotype carriers (pinteraction=0.05). Our findings provide evidence that telomere length and genetic variation in telomere maintenance genes may be associated with risk of lung cancer susceptibility and warrant replication in larger studies.

Summary: Pyrogallol, a catechin compound, is an active component of Emblica officinalis extracts and has an anti-proliferative effect on some human cancer cell lines. In our preliminary study, pyrogallol had highly cytotoxic effect on human lung cancer cell lines and less effect on human bronchial epithelium cell line. This study was performed to investigate the beneficial effect of pyrogallol on human lung cancer cell lines â?? H441 (lung adenocarcinoma) and H520 (lung squamous cell carcinoma). The MTT (cytotoxic) data showed the inhibition growth of lung cancer cells followed pyrogallol treatment. The cell cycle of lung cancer cells was arrested in G2/M phase using flow cytometry. Using Western blot analysis, the cell cycle related proteins â?? cyclin B1 and Cdc25c were decreased in a time-dependent manner and the phosphorylated Cdc2 (Thr14) was increased within 4h pyrogallol treatment. Moreover, the higher cleavage of poly (ADP)-ribose polymerase (PARP), the increased of Bax concurrent with the decreased of Bcl-2 indicated that pyrogallol treatment resulted in apoptosis of lung cancer cells. The cell apoptosis was also directly demonstrated using Annexin V-FITC and TUNEL stain. Additionally, the tumoricidal effect of pyrogallol was measured using a xenograft nude mice model. After 5 weeks of pyrogallol treatment could cause the regression of tumor. Taken in vitro and in vivo studies together, these results suggest that pyrogallol can be developed as a promising anti-lung cancer drug particular for the non-small cell lung cancer (NSCLC).

Abstract: Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis, and its expression is up-regulated in many carcinomas. In the present study, we found that a microRNA miR-126 has a binding site in 3�-untranslated region of the VEGF-A mRNA. In eight lung cancer cell lines, expression of miR-126 was down-regulated. Reporter gene assay showed that the co-transfection of mir-126 expression vector with pLuc-VEGF/mir126BS could reduce the activity of luciferase. Transfection experiments showed that miR-126 could decrease the expression of VEGF-A. Three human lung carcinoma cell lines A549, Y-90 and SPC-A1 were investigated as cancer models in vitro, and A549 infected by lentivirus-miR-126 (LV-miR-126) was studied in tumor xenograft model. Infection of LV-miR-126 can down-regulate the expression of VEGF-A in A549, Y-90 and SPC-A1 cell lines and can inhibit the growth of these cells. In addition, flow cytometry analysis revealed that LV-miR-126 infection can induce cell cycle G1 arrest in A549, Y-90 and SPC-A1 cells. Furthermore, in nude mice, the average weight of A549 tumor nodules in experimental group was reduced from 0.8035±0.1521 to 0.6235±0.0757g, with the inhibitive rate being 22.4%. All these results revealed that miR-126 may have a tumor suppressor function in lung cancer cells and could be a promising treatment in anticancer therapy.

Abstract: Osteopontin (OPN) is a multi-functional cytokine involved in cell survival, migration and adhesion which is associated with tumorigenesis, progression and metastasis. However, the role of OPN in chemo-sensitivity of human lung cancer has not yet been elucidated. The purpose of this study is to investigate the role of OPN in chemo-sensitivity of lung cancer cells. We developed a stable OPN transfectant (SBC-3/OPN) and a control transfectant (SBC-3/NEO) from human small cell lung cancer cell line, SBC-3. SBC-3/OPN cells were more resistant to cisplatin than SBC-3/NEO cells. Multi-drug resistance-associated protein (MRP) does not appear to be involved in the development of acquired chemo-resistance, since MRP inhibitor did not alter chemo-sensitivity. After exposure to cisplatin, the apoptotic SBC-3/OPN cells were reduced in number compared to SBC-3/NEO cells. Treatment with cisplatin revealed that the expression of anti-apoptotic protein, bcl-2, was down-regulated in SBC-3/NEO cells, while that of SBC-3/OPN cells was not altered. In contrast, pro-apoptotic protein, bax, was not altered in both SBC-3/OPN and SBC-3/NEO cells, thus bcl-2/bax ratio was decreased in SBC-3/NEO but not altered in SBC-3/OPN cells. Activation of caspase-3 and caspase-9 was increased in SBC-3/NEO cells, but not in SBC-3/OPN cells. Our results suggest that OPN enhances chemo-resistance of cisplatin in SBC-3 cells by suppressing bcl-2 protein down-regulation, thereby blocking the caspase-9- and caspase-3-dependent cell apoptosis.

Abstract: Malignant pleural mesothelioma (MPM) is a locally aggressive neoplasm, principally linked to asbestos fibres exposure. Strong evidences associate this pollutant with induction of DNA breaks, aberrant chromosomes segregation and important chromosomal rearrangements, considered crucial events in malignant transformation. A considerable contribution to cellular transformation in MPM is also given by the presence of high genomic instability, as well as by the increased DNA methylation, and consequent decreased expression, of tumor-suppressor genes. In this study we first demonstrated that MPM cells are characterized by a decreased methylation level of pericentromeric DNA sequences which can justify, at least in part, the genomic instability observed in this neoplasia. Concomitantly, we found a paradoxical increased expression of DNMT1, the most expressed DNA methyltransferases in MPM cells, DNMT3a and all five isoforms of DNMT3b. Thus, we compared two experimental strategies, DNMT1 silencing and usage of a demethylating agent (5-aza-2â?²-deoxycytidine or Decitabine), both theoretically able to revert the locally hypermethylated phenotype and considered potential future therapeutic approaches for MPM. Interestingly, both strategies substantially decrease cell survival of MPM cells but the antitumor activity of Decitabine, differently from DNMT1 silencing, is mediated, at least in part, by a p53-independent p21 upregulation, and is characterized by the arrest of MPM cells at the G2/M phase of the cell cycle. These results indicate that the two approaches act probably through different mechanisms and, thus, that DNMT1 silencing can be considered an effective alternative to Decitabine for cancer treatment.

Abstract: Incidences of mesothelioma are on the rise in Japan. However, the accurate frequency of mesothelioma occurrence is still unknown. The aim of this study is to clarify the accuracy of pathological diagnosis of mesothelioma. Among the 2742 mesothelioma death cases extracted from the document â??Vital Statistics of Japanâ?? for 2003â??2005, pathological materials were obtained for 382 cases. After these materials were reviewed and immunohistochemical analyses were conducted, mesothelioma was diagnosed by discussions based on clinical and radiological information. Sixty-five cases (17.0%) were categorized as â??definitely not/unlikelyâ?? mesotheliomas, and 273 cases (71.5%) were categorized as â??probable/definiteâ?? mesotheliomas. The percentage of â??probable/definiteâ?? pleural and peritoneal mesothelioma cases in males was 74.3% and 87.5%, respectively, and that of pleural cases in females was 59.2%; however, the percentage of â??probable/definiteâ?? peritoneal cases in females was only 22.2%. These results suggest that the diagnostic accuracy of mesothelioma is relatively low in females and in cases of peritoneal and sarcomatoid subtype mesotheliomas; furthermore, approximately 15% of cases of deaths due to mesothelioma in Japan are diagnostically suspicious.

Abstract: Background: After induction treatment restaging of mediastinal disease in patients with stage III non-small cell lung cancer (NSCLC) may lead to selection of candidates for further surgical treatment. Nodal down-staging is the best predictive characteristic for proceeding with surgery.We report our experience in restaging with endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) and with repeated integrated positron emission tomography and computed tomography (PETâ??CT).Methods: Twenty-eight patients with stage III NSCLC were staged with integrated PETâ??CT, cerebral magnetic resonance imaging (MRI) and pathologically proven nodal disease.Restaging was performed with PETâ??CT and EUS-FNA on the same nodes that showed initially metastatic disease provided these nodal sites determined the tumor stage. Cerebral MRI was not repeated.When restaging EUS-FNA revealed no malignant cells anymore, patients were operated. The postoperative pathologic results were compared with the preoperative restaging EUS-FNA results. Also, patterns of decreased fluoro-2-deoxyglucose (FDG) uptake were compared with the postoperative pathologic results.Results: Restaging EUS-FNA was well tolerated in all patients even in those with clinical signs of radiation esophagitis.Of the 28 patients 15 were down-staged based on cytologic findings with restaging EUS-FNA and in one patient the cytology was not conclusive. Of these 15 patients, down-staging was histologically confirmed after mediastinal exploration in 11 patients and 1 patient had persistent nodal disease at resection. In 3 patients no mediastinal tissue verification was performed. Two subjects were not fit for operation, and in the other patient intraoperative nodal staging was omitted. The negative predictive value for restaging EUS-FNA was 91.6%. The accuracy of EUS-FNA was 92.3%.Concordance between findings of restaging EUS-FNA and metabolic response of lymph node metastases occurred in 17 out of 27 patients.Conclusion: Restaging with EUS-FNA after induction chemo(-radiotherapy) is well tolerated and predicts the absence of nodal metastasis reliably. Although changes in mediastinal FDG-PET uptake show a high concordance with EUS-FNA, pathological confirmation is still superior and therefore necessary. EUS-FNA is the procedure of first choice for mediastinal restaging.

Abstract: Purpose: To evaluate the clinical usefulness of fluorodeoxyglucose (FDG)-PET maximal SUV in combination with CT features for differentiation of adenocarcinoma with bronchioloalveolar carcinoma (BAC) from other subtypes of non-small cell lung cancer (NSCLC).Materials and methods: This retrospective study included 125 patients (104 men and 21 women; mean age, 64 years) who underwent CT and subsequent FDG-PET examinations for preoperative evaluation and underwent curative intent operation with the final diagnoses of NSCLC made by surgical histopathology. We categorized NSCLC into adenocarcinoma with BAC feature and other subtypes. Finally, there were 16 cases of adenocarcinoma with BAC and 109 cases of other NSCLC subtypes included in the study. Several CT features of lung cancer were analyzed, including tumor size, presence of spiculation, margin (irregular or smooth), pattern of the mass (pure solid, pure ground glass opacity and mixed), associated pleural effusion and location (center, mid and periphery). Maximal SUV and visual scores of FDG uptakes of primary NSCLC were evaluated. The diagnostic performances of CT alone, PET alone, and combination of two modalities to predict adenocarcinoma with BAC from other subtypes of NSCLC were calculated.Results: A nodule with a mixed pattern with partly solid and ground glass opacity was significantly more frequent CT feature of an adenocarcinoma with BAC (8/16, 50%) as compared with the other subtypes (2/109, 1.8%) (p<0.0001). Maximal SUV of adenocarcinoma with BAC (mean=7.2) was significantly lower than that of other subtypes of NSCLC (mean=13.33) (p<0.0001). Sensitivity, specificity, PPV, and NPV of CT for differentiating adenocarcinoma with BAC from other subtypes was 50% (8/16), 98.2% (107/109), 80% (8/10), and 93% (107/115), respectively. Sensitivity, specificity, PPV, and NPV of FDG-PET was 68.8% (11/16), 86.2% (94/109), 42.3% (11/26), and 94.9% (94/99), respectively. Sensitivity, specificity, PPV, and NPV of combination of two modalities was 81.3% (13/16), 85.3% (93/109), 44.8% (13/29), 96.9% (93/96), respectively.Conclusion: Careful combined assessment of the FDG-PET maximal SUV and CT findings have the potential to differentiate an adenocarcinoma with BAC from other NSCLC subtypes, such as a pure BAC. These findings might be useful for imaging interpretations and will help initial planning of NSCLC management.

Abstract: The aim of the present study was to investigate the difference in doubling time between squamous cell carcinoma (SCC) and adenocarcinoma of solid pulmonary cancer using three-dimensional volumetric software.We included 40 patients with adenocarcinoma and 11 patients with SCC, who underwent CT examinations more than once before surgical treatment. Tumor volumes and doubling times were obtained using three-dimensional volumetric computer software. Statistical analysis was performed using Mannâ??Whitney's U-test except for negative doubling times (doubling times less than 0 day).Negative doubling time was found in 5 of the 40 adenocarcinomas (13%), but not in any of the patients with SCC. Doubling time was beyond 400 days in 11 of the 40 adenocarcinomas (28%), but was always less than 400 days in SCC. The mean doubling time of SCC was 126±58 days (range, 39â??221 days; median, 131 days), while that of adenocarcinomas, except for the negative doubling times, was 976±3134 days (range, 69â??18,678 days; median, 258 days). Doubling time differed significantly between adenocarcinomas and SCC (p<0.01).In conclusion, the median doubling time of SCC lung cancers is less than that of adenocarcinomas, as measured with automated volumetric measurement software.

Abstract: Background: Although it is recommended that smokers undergoing surgery for lung cancer quit smoking to reduce post-operative complications, few studies have examined patterns of smoking in the peri-operative period. The goals of this study were to determine: (1) patterns of smoking during post-operative recovery, (2) types of cessation strategies used to quit smoking, and (3) factors related to smoking after lung cancer surgery.Methods: Data were collected from 94 patients through chart review, tobacco, health status, and symptom questionnaires at 1, 2, and 4 months after surgery. Smoking status was assessed through self-report and urinary cotinine measurement.Results: Eighty-four patients (89%) were ever-smokers and 35 (37%) reported smoking at diagnosis. Thirty-nine (46%) ever-smokers remained abstinent, 13 (16%) continued smoking at all time-points, and 32 (38%) relapsed. Ten (46%) of those who relapsed were former-smokers and had not smoked for at least 1 year. Sixteen (46%) of those who were smoking at diagnosis received cessation assistance with pharmacotherapy being the most common strategy. Factors associated with smoking during recovery were younger age and quitting smoking â?¤6 months before the diagnosis of lung cancer. Factors that were marginally significant were lower educational level, male gender, lower number of comorbidities, and the presence of pain.Conclusion: Only half of those who were smoking received assistance to quit prior to surgery. Some patients were unable to quit and relapse rates post-surgery were high even among those who quit more than 1 year prior. Innovative programs incorporating symptom management and relapse prevention may enhance smoking abstinence during post-operative care.

Abstract: Purpose: To test toxicity, tolerability, time to progression, survival and response rate in the 3-day administration of topotecan (T) followed by carboplatin (C), and then etoposide (E) in a study for small cell lung cancer (SCLC) treatment.Patients: 44 chemotherapy-naive patients with SCLC (median age 63.5, PS 0â??1). ED was present in 28 patients.Methods: Each treatment cycle consisted of T (0.8mg/m2 on days 1â??3), C (AUC=5, day 3) and a standard oral dose of E (100mg on days 15â??17). Cycles were repeated every 32 days and up to eight were performed. Responders received radiotherapy to the primary site (50Gy) after the 4th cycle and complete responders also received PCI.Results: Complete response (CR) was achieved in 4 patients, partial response (PR) in 18, stable disease in 10 and PD in 12. Median survival was 280 (±36.7) days and median time to progression 137 days. 11 patients developed grade 3/4 neutropenia and 3 patients grade 3/4 anaemia. Non-haematological toxicity was mild.Conclusion: In contrast to ORR, PFS and survival were quite similar to those of SCLC patients suffering from ED treated by a platinumâ??etoposide regimen. The T/C/E combination was well tolerated and with low toxicity, but without improvement in the ORR and survival in comparison to platinum analogue regimes.

Abstract: The aim of this study was to investigate the relation of HLA alleles in patients with non-small cell lung cancer (NSCLC).The incidence of class I and II HLA alleles of 63 patients with NSCLC were prospectively compared with the incidence of class I and II HLA alleles with 88 healthy controls. The number of cases with stage I and II (early stage) was 12 and there were 51 cases with stage III and IV (advanced stage). Metastasis rates of the regional lymph node in patients were as follow; N0: n=10; N1: n=13; N2: n=26 and N3: n=14. Lymph node metastasis was detected by pathological staging in 15 cases and by clinical staging in 48 cases. Lymph node metastasis was searched in all patients by a helical thorax CT. All distant metastasis were investigated by thorax CT, abdominal CT, brain CT or MRI and bone scintigraphy, and distant organ metastasis was detected in 25 cases. The patients and healthy controls were typed for HLA class I and II alleles.HLA-A2 was an independent risk factor for both critical lymph node (N2 and 3) involvement and distant metastasis. HLA-B44, -CW6 and -CW7 frequencies appear to be significant in controls compared to patients. HLA-A2 frequency was higher in patients with advanced stage than early stage, while HLA-A26, -B35 and -CW4 frequencies were more expressed in patients with early stage than in patients with advanced stage. Compared with controls, frequency of HLA-DRB1*07, -DQ02 and -DQ07 were lower expressed in patients. Compared patients with advanced stage, HLA-DRB1*07 was higher in patients with early stage.HLA-A2 was an independent risk factor for lymph node and distant metastasis, and the allele was significantly higher in patients with critical lymph node for surgery and distant metastasis. HLA-A26 appeared to be a significance protective allele against to metastases.

Abstract: Background: Eukaryotic initiation factor 4E (eIF4E), an important regulator of translation, plays important roles in tumor transformation, progression and metastasis. However, the clinical significance of eIF4E expression in lung adenocarcinoma (AdC) remains unclear. The aim of this study was to explore the expression of eIF4E gene in lung adenocarcinoma cell lines and tissues, and to investigate its relationship with clinical characteristics and prognosis of patients with lung adenocarcinoma in combination with p53 status.Methods: Semi-quantitative RT-PCR and Western blotting assays were performed to detect the expression of eIF4E mRNA and protein in normal human lung epithelial cell line, immortalized lung epithelial cell line and lung adenocarcinoma cell lines. Additionally, the expression of eIF4E gene was also detected in 32 cases of lung adenocarcinoma tissues, tumor adjacent tissues and tumor surrounding normal tissues by the same methods. Moreover, expression of eIF4E and the status of p53 in specimens from 76 patients with lung adenocarcinoma were examined by immunohistochemical staining. Correlations between eIF4E expression and clinicopathological features, and the effect of eIF4E on prognosis of patients with lung adenocarcinoma were evaluated by statistical analysis.Results: The levels of eIF4E mRNA and protein expression were higher in lung adenocarcinoma cell lines and in telomerase-immortalized lung epithelial cell line than in the normal lung epithelial cell line. The expression of eIF4E gene showed statistical difference between tumor tissues, tumor adjacent tissues and tumor surrounding normal tissues (P<0.05). Moreover, the higher levels of eIF4E expression were correlated with poorer differentiation (P=0.012), higher pathological stage (P<0.0001) and clinical stage (P=0.002), a higher incidence of hematogenous metastasis (P=0.007) and cancer-related death (P=0.036). The 5-year survival rate of patients with higher eIF4E expression was significantly lower than that of patients with lower eIF4E expression (P=0.0045). Furthermore, in a multivariate analysis by Cox regression model, high eIF4E expression was confirmed to be an independent prognostic factor (HR: 2.258; unfavorable, P=0.0056), while lymph node (HR: 2.033; unfavorable, P=0.0440) and hematogenous metastasis (HR: 3.489; unfavorable, P<0.0001) were also significant prognostic factors.Conclusion: High eIF4E expression was correlated with poorer overall survival in lung adenocarcinoma patients. eIF4E might be a better clinical marker predicting the prognosis for lung adenocarcinoma patients in combination with p53 status.

Abstract: Previous studies have suggested aberrant expression of membrane B7-H3 in tumor cells. This aim of the study was to determine the expression level of soluble B7-H3 (sB7-H3) in circulation and to subsequently evaluate the clinical significance of circulating B7-H3 in patients with non-small cell lung cancer (NSCLC). The level of circulating B7-H3 was determined with ELISA and its correlation with the clinical data was examined. Receiver operating characteristic (ROC) curve analysis was performed to compare the sensitivity and specificity in the diagnosis of NSCLC. Circulating B7-H3 levels in patients with NSCLC were significantly higher than those in patients with other pulmonary diseases (OPD, p<0.001), or those in healthy volunteers (p<0.001). Using a cutoff of 30ng/ml, the sensitivity and specificity of sB7-H3 in differentiating between patients with NSCLC and patients with OPD, and between patients with NSCLC and healthy volunteers was, 48.8 and 98.5%, and 48.0 and 93.7%, respectively. Additionally, higher levels of sB7-H3 were associated with higher tumor stage, tumor size, nodal metastasis, and distant metastasis, but not with sex, age or histological subtype. An area under the curve (AUC) for all stages of NSCLC resulting from sB7-H3 (0.862), which was significantly better than any other tumor markers tested including CA125 (0.621), CA153 (0.571), CA199 (0.459), and CEA (0.638). These results suggest circulating B7-H3 is a valuable biomarker for NSCLC and an elevated level of circulating B7-H3 suggests a poor clinical character for NSCLC.

Abstract: This multicenter, non-interventional, prospective, observational study aimed to determine whether patientsâ?? attitude to chemotherapy is an independent prognostic factor for survival in patients with advanced non-small cell lung cancer (NSCLC) who are treated with gemcitabineâ??platinum. Chemonaive patients (n=1895) with stage IIIB or IV NSCLC not amenable to curative surgery or radiotherapy were treated with a combination of gemcitabine plus cisplatin/carboplatin and followed for a maximum of 18 months. Patientsâ?? attitude to treatment was measured on a 5-point scale and responses were used to assign patients to one of the three need categories: A, maximum extension of survival with the acceptance of high toxicity (60.0% of patients); B, maximum extension of survival only if coupled with normal lifestyle (26.1%); C, relief of symptoms (13.8%). Median survival varied significantly among the need categories (A=13.00 months, B=15.70 months, C=15.33 months; log-rank test P=0.0415). Patient attitude to treatment (need categories) was not a significant prognostic factor for survival after adjusting for known prognostic factors (P=0.0503). After adjusting for baseline differences, patients in this study had a significantly lower risk of death than patients in three randomized trials (hazard ratio 0.879; 95% confidence interval: 0.775, 0.998; P=0.0458). In conclusion, in this observational study, patient attitude to chemotherapy was not an independent prognostic factor of survival.

Summary: Background: Inhibition of the EGFR pathway is a useful strategy in the treatment of patients with advanced NSCLC. The aim of this study is to assess predictive clinical parameters of efficacy.Methods and patients: Sixty-two patients with advanced NSCLC were treated with erlotinib as secondâ??third line (150mg/day). Baseline patient characteristics were: performance status (PS) 1: 92%; median age, 58 years; males, 73%; adenocarcinoma, 45%; current/former smokers, 83%. During erlotinib treatment, 35% of patients had no rash, 32.3% had grade 1 rash, 26% had grade 2 rash and 6.5% patients developed grade 3 rash.Results: For patients with grades 2â??3 rash vs. those with grades 0â??1 rash, time to tumor progression (TTP) and overall survival (OS) were 92 vs. 41 days (p=0.0381) and 244 vs. 131 days (p=0.011), respectively. For patients with non-smoking history and current/former smokers, TTP and OS were 136 vs. 42 days (p=0.0015) and 324 vs. 133 days (p=0.0242), respectively. In addition, rash grade and smoking history were found to have a highly significant impact on TTP and OS, according to the Cox model.Conclusions: Grade â?¥2 rash and non-smoking history are associated with improved TTP and OS in advanced NSCLC patients treated with erlotinib.

Abstract: Background: Women with non-small cell lung cancer (NSCLC) appear to have better survival. This study aimed to evaluate sex differences in NSCLC in recent years. The true effect of gender on the overall survival was analyzed taking other prognostic factors into account.Methods: A cohort of consecutive NSCLC patients was prospectively enrolled from January 2002 to December 2005, and followed-up until December 2006. They were clinically and pathologically staged and underwent homogenous treatment algorithms. Demographics, histology, and disease stage between sexes were compared. The clinical prognostic factors to be analyzed in addition to gender included stage, age, smoking history and histology. The overall survival of females and males within relevant subgroups defined by smoking history and histology was also compared.Results: Of the 738 patients, 695 were analyzed with a definite stage (94.2%; 315 females and 380 males), which was similar in both sexes. Females were younger (median age: 59.5 years vs. 65.0 years; P<0.001) and more likely to have adenocarcinoma (81% vs. 60.5%; P<0.001). Patients with earlier stage, younger patients, never-smokers and females had better overall survival in univariate analyses and no significant survival difference was noted between adenocarcinoma and squamous cell carcinoma. Multivariate analyses demonstrated age, smoking history and gender to have a hazard ratio 1.46 (95% confidence interval, CI 1.21â??1.76; P<0.001), 1.27 (95% CI 0.97â??1.65; P=0.082), and 1.18 (95% CI 0.90â??1.55; P=0.226), respectively. Subgroup analyses revealed the survival of never-smoker males with adenocarcinoma was similar to that of females.Conclusions: There are sex-related differences in the clinico-pathologic characteristics and survival of NSCLC patients. The survival advantages of females could be attributed to the younger age and lower smoking prevalence. Never-smokers with adenocarcinoma should be given special attention regardless of sex as they imply better survival with different treatment outcomes.

We have previously reported results of our own experience with pulmonary rehabilitation (PR) in pre- and post-operative settings of surgical cohorts of non-small cell lung cancer (NSCLC) patients.

We read with great interest the recent publication by Carteni et al. who reported the results of an International Expanded Access Program that allowed the compassionate use of Pemetrexed (PEM) for patients with malignant peritoneal mesothelioma (MPM) through a pharmaceutical company sponsored and FDA approval scheme. Under this scheme, 109 patients received PEM treatment for MPM. This is by far the largest study of patients receiving systemic chemotherapy for MPM. In 2003, the role of PEM in combination with Cisplatin was established through a Phase III randomized trial that reported a median survival of 12.1 months in the combination PEM and Cisplatin arm over 9.3 months in the Cisplatin alone arm (p=0.02) . The success of PEM led to a worldwide approval and recognition of the role of PEM in mesothelioma. However, it has been estimated that although pleural mesothelioma accounts for majority of all mesothelioma, a third of patients develop mesothelioma from the serous layer of the peritoneum only. This disease is termed MPM. It has been assumed that the disease aetiology governing the underlying molecular and biological carcinogenesis pathway is mostly similar and hence a rationale role of the use of PEM in MPM based on the results of the randomized trial.

Biomarker assessment might improve the diagnostic algorithms used for lung cancer screening with low-dose spiral computed tomography (LDSCT) . In previous caseâ??control studies of clinically detected lung cancers, we showed that high levels of free circulating plasma DNA are strongly associated with the presence of lung cancer independently of tumor stage .

Abstract: In the study of Steinfort et al., as well as in previous studies, no cases of co-involvement of malignant features and sarcoidal reactions were seen in non-small cell lung cancer patients undergoing mediastinal staging, leading the authors to state that non-necrotizing granulomas revealed by EBUS-TBNA should serve to indicate the absence of lymph node metastases. We report on a case of stage IIIA pulmonary adenocarcinoma in which TBNA of a subcarinal node showed the presence of both neoplastic cells and non-necrotizing granulomas.

We thank Trisolini et al. for their interest in our manuscript, and their contribution to the literature, with description of a patient in whom transbronchial needle aspiration (TBNA) of a subcarinal lymph node revealed both adenocarcinoma and non-necrotising granulomas . We agree this is significant following our recent publication in which we concluded â??Non-necrotising granulomas revealed by EBUS-TBNA of lymph nodes during staging of non-small cell carcinoma (NSCLC) should serve to indicate the absence of lymph node metastasesâ?? .