MDM2 Polymorphism, Survival, and Histology in Early-Stage Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (16) ◽  
pp. 2243-2247 ◽  
Author(s):  
Rebecca Suk Heist ◽  
Wei Zhou ◽  
Lucian R. Chirieac ◽  
Thea Cogan-Drew ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Log Rank Test ◽  
Mdm2 Polymorphism

Purpose MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common. Patients and Methods We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non–small-cell lung cancer (NSCLC) treated with surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan-Meier methods and the log-rank test were used to compare survival by polymorphism status. Cox proportional hazards models were used to adjust for possible confounding variables. Results There were 383 patients in the analysis. In the early-stage population as a whole, the G/G genotype seemed to be associated with worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% CI, 1.03 to 2.40; P = .04). Among patients with squamous histology, OS was significantly worse among those with the G/G genotype (P = .0001 by log-rank test), with 5-year survival rates among the genotypes of 59% for T/T, 53% for T/G, and 7% for G/G. Conclusion Our findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology.

Improving survival for metastatic non-small cell lung cancer: A SEER database analysis from 1990 to 2005

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8078-8078
Author(s):  
D. Morgensztern ◽  
S. N. Waqar ◽  
F. Gao ◽  
R. Govindan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Female Gender ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Eligibility Criteria

8078 Background: Treatment of metastatic non-small cell lung cancer (NSCLC) has evolved over the last decade with the increased use of third-generation chemotherapy agents, established benefits from second-line chemotherapy, and the development of targeted agents. We conducted a study to evaluate whether these treatment advances translated into improved survival in a large registry database. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 or older, and diagnosed between 1990 and 2005. Overall Survival (OS) rates were estimated by the Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was fitted to evaluate whether the diagnostic period is an independent predictor for OS. Demographic variables included period of diagnosis (1990–1993 or P1, 1994–1997 or P2, 1998–2001 or P3, and 2002–2005 or P4), age, gender, race, and histology. Results: There were 127,816 patients meeting eligibility criteria. Median age at presentation was 67 and most patients were male (58%), white (81%), and had adenocarcinoma (39%). Although there was no significant differences in OS between periods 1 and 2 (p = 0.18), there was a significant improvement from periods 2 to 3 (p < 0.001) and 3 to 4 (p < 0.001). 1-y and 2-y OS increased from 13.2% and 4.5% respectively in P1 to 19.4% and 7.8% respectively in P4. Predictive factors for improved survival in multivariate analyses included diagnostic period (p < 0.001), younger age (p < 0.0001), female gender (p < 0.0001), and non-black race (p < 0.0001). After adjusting for demographic factors, there were no significant differences in OS between adenocarcinoma and squamous cell from P1 to P3 (1990–2001). However, P4 showed a significant increase in OS for adenocarcinoma compared with squamous cell (p = 0.02). Conclusions: There has been a significant improvement in OS for stage IV NSCLC over the last 8 years. The recent differences in outcomes based on histology observed in P4 may reflect the increased activity of newer therapies in adenocarcinoma compared with squamous cell, including gefitinib and erlotinib. No significant financial relationships to disclose.

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non–Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy

2000 ◽  
Vol 18 (10) ◽  
pp. 2095-2103 ◽  
Author(s):  
Frances A. Shepherd ◽  
Janet Dancey ◽  
Rodryg Ramlau ◽  
Karin Mattson ◽  
Richard Gralla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Supportive Care ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Log Rank Test ◽  
Platinum Based Chemotherapy

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m 2 . Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Clinical significance of altered expression of the retinoid acid receptors alfa and beta (RAR a and b) and the cellular retinol binding protein (CRBP-1) in stage I non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18117-18117
Author(s):  
M. G. Pallotta ◽  
L. Mauro ◽  
G. Z. Beguelin ◽  
L. M. Dallurzo ◽  
D. Smith ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Habit ◽  
Small Cell ◽  
Stage I ◽  
Rank Test ◽  
Small Cell Lung ◽  
Altered Expression ◽  
Log Rank Test

18117 Background: Retinoids, a group of natural and synthetic Vitamin A analogues, are known to play a major role in regulating growth, differentiation and apoptosis of many cell types. Its role as prognostic factors in non-small cell lung cancer (NSCLC) is poorly known. Methods: Patients who underwent a successful surgical resection for stage I NSCLC were elegible. Antigen expression was analyzed by immuno histochemistry on histological samples of the tumor to investigate the expression pattern of RARa, RARb and CRBP-1. 51 NSCLC patients stage I (18 Stage Ia and 33 Stage Ib) were tested . A case was considered positive when more than 10% of cells presented specific staining for the antigen. Prognostic evaluation was performed with the Log-Rank test and the multivariate proportional hazard model. Results: About 40% of cases were positive for RARa. In the case of RARb 58.3% NSCLC showed cytoplasm staining, while only 18% showed nuclear immunopositivity. Taken together, the 81.5% of NSCLC tumors expressed at least one RA receptor (RARa or RARb or both). CRBP-1 staining was observed in 52% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T stage, histopathology, adjuvant therapy, smoking habit or the presence of tumor cells in the pleural fluid. The only exception was that a higher percentage of adenocarcinomas were positive for RARa as compared with epidermoid tumors (50.0 vs 14.3%, p=0.05). On the other hand RARb was expressed preferentially in epidermoid tumors (81.3% vs 42.9 %, p<0.05). Univariate analysis showed a significant association between positive expression of RARb with shorter overall survival (log-rank test 3.7, p<0.05). However, the multivariate study indicated that RARb expression was influenced by other clinical pathological parameters, suggesting that this antigen would not be able to predict cancer-specific survival in an independent way. Conclusions: A high number of stage I NSCLC express RARs and CRBP. This suggests that retinoid expression could harbour relevant prognostic information at an early stage of the disease. No significant financial relationships to disclose.

VEGFPolymorphisms and Survival in Early-Stage Non–Small-Cell Lung Cancer

2008 ◽  
Vol 26 (6) ◽  
pp. 856-862 ◽  
Author(s):  
Rebecca Suk Heist ◽  
Rihong Zhai ◽  
Geoffrey Liu ◽  
Wei Zhou ◽  
Xihong Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Massachusetts General Hospital ◽  
Early Stage ◽  
Small Cell ◽  
Rank Test ◽  
Survival Outcomes ◽  
Small Cell Lung ◽  
Vegf Polymorphisms

PurposePolymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non—small-cell lung cancer (NSCLC) patients.Patients and MethodsWe evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C>T (rs3025039), −460T>C ( rs833061 ), and +405G>C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test.ResultsThere were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G>C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P = .006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P = .008). Five-year OS for patients carrying the variant C allele of the VEGF +405G>C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C>T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P = .07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P = .07). Moreover, patients with higher number of variant alleles of the +405G>C and +936C>T polymorphisms had better survival. There was no association found with the −460T>C polymorphism.ConclusionPolymorphisms in VEGF may affect survival in early-stage lung cancer.

STEREOTACTIC BODY RADIATION THERAPY FOR EARLY-STAGE NON-SMALL CELL LUNG CANCER

2018 ◽  
Vol 64 (5) ◽  
pp. 638-644
Author(s):  
Andrey Arsenev ◽  
Sergey Novikov ◽  
Sergey Kanaev ◽  
Anton Barchuk ◽  
Andrey Nefedov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stereotactic Radiation ◽  
Screening Programs ◽  
Surgical Methods

An active introduction of screening programs potentially leads to a significant increase in the proportion of patients with early forms of non-small cell lung cancer. Surgical treatment, which is the standard of care for localized forms, due to functional limitations can be performed only in 65-70% of patients. The solution to this problem can be found in the improvement of the results of radiotherapy by using modern equipment, the planning systems, improved fractionation schemes and introduction of methods for summing radiation doses. Stereotactic radiotherapy allows high-precision delivery of high radiation dose to tumor with a minimal damage to surrounding healthy tissues. In this literature review based on the analysis of a large number of publications we show that it is not yet possible to make valid conclusions about the effectiveness and safety of stereotactic radiation therapy as an alternative to the surgical methods. It is necessary to plan and conduct randomized trials without further delay taking into account the expected high relevance of the method.

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