The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 loci on the risk and prognosis of Portuguese patients with non-small cell lung cancer

Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND METHODS: Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF -460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p?=?0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p?=?0.042; rs3025010 (VEGF intron 5 C/T), p?=?0.047; rs401681 C/T at 5p15, p?=?0.046; and rs31489 C/A at 5p15, p?=?0.029. CONCLUSIONS: Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.This project was supported by Programa Doutoral em Medicina e Oncologia Molecular, University of Porto, Porto, Portugal and University of Minho, Braga, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Progress in the management and outcome of small-cell lung cancer in a French region from 1981 to 1994

Recent analyses of series of small-cell lung cancer (SCLC) patients included in clinical trials have shown improved survival over time, but it has been impossible to determine whether this was due to selection biases, stage migration, or true therapeutic improvement. To determine if there has been a true improvement of survival over time, we reviewed the medical records of all consecutive patients diagnosed with SCLC between 1981 and 1994 in the Bas-Rhin in France. Among the 787 patients (median age 63), there was no significant period effect for sex, age, or stage. Staging work-ups became increasingly thorough (significant period effect). The mean number of investigations and of tumour sites detected correlated significantly. The chemotherapy rate increased (from 76.4% in 1981–1983 to 91.7% in 1993–1994, P = 10−5) and mediastinal irradiation decreased (to roughly 25% of patients after 1983). Median survival time increased for the overall population from 6.6 months in 1981–1983 to 11.3 months in 1993–1994 (P = 10−5), for patients with limited disease (LD) from 9.2 (P = 0.002) months to 14.0 months, and for those with extensive (ED) disease from 3.5 months to 9.6 months (P = 10−5). Significant independent prognostic factors were disease extent, clinical trial participation, period, type of chemotherapy, and mediastinal irradiation in LD. Survival time has truly improved as ‘state of the art' management of SCLC has changed. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC) with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

<p>Abstract</p> <p>Background</p> <p>Second-line treatment of advanced non-small-cell lung cancer (NSCLC) improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS) and health-related quality of life (HR-QoL) during second-line pemetrexed treatment in routine clinical practice.</p> <p>Methods</p> <p>Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation) were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI) of ≥ 10% (absolute) or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response"). HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D). Factors potentially associated with KI benefit response were evaluated using logistic regression models.</p> <p>Results</p> <p>Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%), 471 (90.4%) completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2%) achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%).</p> <p>Conclusions</p> <p>In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years), physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients.</p> <p>Trial registration</p> <p>Registered on ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540241">(NCT00540241)</a> on October 4, 2007</p