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.

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.

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.

Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small cell lung cancer

2018 ◽  
Vol 23 (3) ◽  
pp. 419-426 ◽  
Author(s):  
Hiroaki Kuroda ◽  
Tatsuya Yoshida ◽  
Takaaki Arimura ◽  
Tetsuya Mizuno ◽  
Noriaki Sakakura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Habit ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung

scholarly journals Preoperative nivolumab to evaluate pathological response in patients with stage I non-small cell lung cancer: a study protocol of phase II trial (POTENTIAL)

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e043234
Author(s):  
Atsushi Kagimoto ◽  
Yasuhiro Tsutani ◽  
Takahiro Mimae ◽  
Yoshihiro Miyata ◽  
Norihiko Ikeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Small Cell ◽  
Pathological Response ◽  
Stage I ◽  
Small Cell Lung

IntroductionRecently, inhibition of programmed cell death 1 or its ligand has shown therapeutic effects on non-small cell lung cancer (NSCLC). However, the effectiveness of preoperative nivolumab monotherapy for stage I NSCLC remains unknown. The present study aimed to investigate the pathological response of preoperative treatment with nivolumab for clinically node negative but having a high risk of NSCLC recurrence.Methods and analysisThe Preoperative Nivolumab (Opdivo) to evaluate pathologic response in patients with stage I non-small cell lung cancer: a phase 2 trial (POTENTIAL) study is a multicentre phase II trial investigating efficacy of preoperative nivolumab for clinical stage I patients at high risk of recurrence. This study includes histologically or cytologically confirmed NSCLC patients with clinical N0 who were found on preoperative high-resolution CT to have a pure solid tumour without a ground-glass opacity component (clinical T1b, T1c or T2a) or a solid component measuring 2–4 cm in size (clinical T1c or T2a). Patients with epidermal growth factor receptor (EGFR) mutation (deletion of exon 19 or point mutation on exon21, L858R), anaplastic lymphoma kinase (ALK) translocation or c-ros oncogene 1 (ROS-1) translocation are excluded from this study. Nivolumab (240 mg/body) is administrated intravenously as preoperative therapy every 2 weeks for three cycles. Afterward, lobectomy and mediastinal lymph node dissection (ND 2a-1 or ND 2a-2) are performed. The primary endpoint is a pathological complete response in the resected specimens. The secondary endpoints are safety, response rates and major pathological response. The planed sample size is 50 patients. Patients have been enrolled since April 2019.Ethics and disseminationThis trial was approved by the Institutional Review Board of Hiroshima University Hospital and other participating institutions. This trial will help examine the efficacy of preoperative nivolumab therapy for clinical stage I NSCLC.Trial registration numberjRCT2061180016.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Tumor cellular proliferation is associated with enhanced immune checkpoint expression in stage I non–small cell lung cancer

2019 ◽  
Vol 158 (3) ◽  
pp. 911-919.e6 ◽  
Author(s):  
Kyle G. Mitchell ◽  
Edwin R. Parra ◽  
David B. Nelson ◽  
Jiexin Zhang ◽  
Ignacio I. Wistuba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Cellular Proliferation ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung
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