-
[show abstract]
[hide abstract]
ABSTRACT: Lymph node metastasis is a major prognostic factor in resected non-small cell lung cancer (NSCLC). However, 30-40 % rate of recurrence after performing complete resection in node-negative patients suggests that their nodal staging is suboptimal. We aimed to evaluate the molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with node-negative NSCLC. Primary tumor samples from 62 patients with resected stage I-IIB NSCLC were screened for fragile histidine triad (FHIT) and CDKN2A mRNA deletion using reverse transcriptase polymerase chain reaction (RT-PCR). The molecular alternations were found in tumors of 49 patients. A total of 269 lymph nodes from these 49 NSCLC patients with FHIT or/and CDKN2A deletion tumors were examined. Fifteen positive-control nodes and ten negative-control nodes were also analyzed for FHIT and CDKN2A mRNA deletion. Thirty-nine (22 %) and 22 (18 %) lymph nodes from the 49 patients with FHIT and CDKN2A mRNA deletion in primary tumor had FHIT and CDKN2A mRNA deletion, respectively. The types of FHIT and CDKN2A mRNA deletion in lymph nodes were identical with those in their primary tumors. By combination of two markers, 16 patients (32.7 %) were found to have nodal micrometastasis. Survival analysis showed that patients with nodal micrometastasis had reduced disease-free survival (P = 0.001) and overall survival (P = 0.002) rates. Multivariate analysis demonstrated that nodal micrometastasis was an independent predictor for worse prognosis. Thus, the detection of lymph node micrometastasis by FHIT and CDKN2A mRNA deletion RT-PCR will be helpful to predict the recurrence and prognosis of patients with completely resected stage I-IIB NSCLC.
Tumor Biology 01/2013; · 1.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Survivin and livin, which are members of the inhibitor of apoptosis protein family, regulate both programmed cell death and proliferation. Second mitochondria-derived activator of caspase is thought to regulate apoptosis by antagonizing inhibitor of apoptosis protein. These gene expressions are regarded as prognostic markers in some malignancies. However, result in previous studies of the association of these gene expressions with prognosis of patients with non-small cell lung cancer remains contradictory.
Survivin, livin and second mitochondria-derived activator of caspase mRNA was detected by semi-quantitative reverse transcriptase-polymerase chain reaction in surgical resected tumor specimen from 66 non-small cell lung patients who received adjuvant platinum-based chemotherapy.
Results showed that patients with survivin high expression had significantly shorter tumor-free survival (P = 0.012) and overall survival (P = 0.007) than those with survivin low expression. There was a significant association of second mitochondria-derived activator of caspase high expression in non-small cell lung cancer tissue with longer tumor-free survival (P = 0.021) and overall survival (P = 0.0013). However, livin mRNA expression level had no impact on the tumor-free survival and overall survival of the patients. In multivariate analyses, survivin mRNA high expression (P = 0.033 and P = 0.024) and advanced pathologic stage (P = 0.009 and P = 0.008) were the factors which independently predicted a worse tumor-free survival and overall survival.
Our data suggest that assessment of survivin and second mitochondria-derived activator of caspase mRNA expression may be useful for predicting survival in non-small cell lung cancer patients receiving platinum-based chemotherapy after surgical resection and can provide valuable information for deciding better therapy strategy.
Japanese Journal of Clinical Oncology 04/2010; 40(4):327-35. · 1.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the efficacy of current chemoradiotherapy on improvement of survival in patients with superior sulcus non-small cell lung cancer (NSCLC).
We retrospectively reviewed the data of 39 patients with superior sulcus NSCLC treated with induction therapy followed surgery. The patients were divided into two groups according to the induction approach: the induction radiotherapy (RT) group (1993-1999), and the induction chemoradiotherapy (CT/RT) group (since 1999).
The rate of complete resection was 65 percent in the RT group (n = 17) compared with 91 percent in the CT/RT group (n = 22, P = 0.024). Complete pathological responses from induction therapy were 12 percent in the RT group and 45 percent in the CT/RT group (P = 0.032). Overall survival (OS) was significantly longer in patients who received CT/RT than that in those who received RT, with 2- and 5-year survival rates of 77.3 percent and 36.4 percent versus 41.2 percent and 11.8 percent, respectively (P = 0.007). CT/RT also associated with a markedly longer tumor-free survival (TFS), with a median TFS of 40 and 17 months, respectively (P = 0.007). Patients achieved complete resection or complete pathological response had a significantly better survival than those with incomplete resection or pathological partial responses and no change (P < 0.0005 and P = 0.001, respectively).
Our results indicate that CT/RT followed by surgery can significantly improve OS and TFS, and may be considered as an optimal option in treatment of patients with superior sulcus NSCLC.
Asia-Pacific Journal of Clinical Oncology 03/2010; 6(1):57-65. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP) and excision repair cross-complementing 1 (ERCC1) in patients with locally advanced non-small cell lung cancer (NSCLC) who received neoadjuvant cisplatin-based chemotherapy.
Transbronchial biopsy (TBB) specimens from 46 patients with stage IIIA (N(2)) NSCLC were collected to determine the expression level of MRP1, BCRP, LRP and ERCC1 mRNA by semiquantitative RT-PCR. The expression level of each gene was analyzed in relation to histopathologic response to chemotherapy, and tumor-free survival (TFS) and overall survival.
Patients with MRP1 or LRP low expression had a significantly better histopathologic response (P=0.032 and 0.006), and a significantly longer TFS (P=0.043 and 0.025) and overall survival (P=0.019 and 0.013) than those with MRP1 or LRP high expression. Patients with ERCC1 low expression had a significantly longer overall survival (P=0.007), but not TFS (P=0.094) than those with ERCC1 high expression. In multivariate analysis, LRP low expression was a significantly favorable factor for TFS (P=0.027), and LRP and ERCC1 were significantly favorable factors for overall survival (P=0.012 and 0.032).
Assessment of MRP1 and LRP mRNA expression in TBB specimens may predict histopathologic response and survival in locally advanced NSCLC patients who received neoadjuvant cisplatin-based chemotherapy. ERCC1 expression was predictive for overall survival.
Lung cancer (Amsterdam, Netherlands) 10/2009; 69(1):116-22. · 3.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prognosis of stage IIIA N2 non-small cell lung cancer (NSCLC) remains poor despite the changes in therapeutic strategies.
To assess long term results of neo adjuvant therapy followed by surgery for patients with stage IIIA N2 NSCLC and to analyze factors influencing survival.
The methods adopted include: Retrospective review of medical records of 91 patients with stage IIIA N2 NSCLC, who received neo adjuvant therapy followed by surgery; collection of information on demographic information, staging procedure, preoperative therapy, clinical response, type of resection, pathologic response of tumor, status of lymph nodes and adjuvant chemotherapy; survival analysis by Kaplan-Meier and calculation of prognostic factors using log-rank and Cox regression model.
All patients received a platinum-based chemotherapy and 23 (29.1%) had an associated radiotherapy. Eighty four patients underwent thoracotomy. Median survival was 26 months (95%CI, 22.6-30.8 months) with three and five year survival rates of 31.6 and 20.9%, respectively. Prognostic factors for survival on univariate analysis was clinical response (P = 0.032), complete resection (P = 0.002), pathologic tumor response ( P < 0.001), and lymph nodal down staging (P = 0.001). Multivariate analyses identified complete resection, pathologic tumor response and lymph nodal down staging as independent prognostic factors.
Survival of patients with stage IIIA N2 NSCLC who received neo adjuvant therapy is significantly influenced by clinical response, complete resection, pathologic tumor response, and lymph nodal down staging. These results can be helpful in guiding standard clinical practice and evaluating the outcome of neo adjuvant therapy followed by surgery in patients with stage IIIA N2 NSCLC.
Annals of thoracic medicine. 10/2009; 4(4):201-7.
-
[show abstract]
[hide abstract]
ABSTRACT: The survival rates for stage IIIA and stage IIIB non-small-cell lung cancer (NSCLC) are extremely poor with single-treatment modalities such as radiation therapy or surgery. The purpose of this study is to assess tolerability, response, surgical resectability, and survival of chemotherapy followed by chemoradiation therapy, and then followed by surgery in patients with stage IIIA (N2-bulky) or stage IIIB NSCLC.
Forty-eight patients with stage IIIA (N2-bulky) or stage IIIB (T4 N1-2 M0) NSCLC received 2 cycles of chemotherapy with cisplatin, mitomycin, and vindesine, subsequent radiation therapy (45 Gy, twice-daily 1.5 Gy) with simultaneous low-dose cisplatin and vindesine, followed by surgery.
Forty-five patients completed induction chemoradiation therapy. Thirty-three patients (68.8%) had clinical response to induction treatment. Thirty-nine patients underwent a thoracotomy, with a complete resection rate of 62.5% (30/48). The pathologic response rate was 60% (27/45), with complete pathologic response of 8 patients. The median survival time for the total group of 48 patients was 23 months, with 3- and 5-year survival rates of 41.7% and 31.8%, respectively. Multivariate analysis showed that complete resection and pathologic response in surgical specimens were independent predictors of survival (P=.048 and P=.022).
Preoperative sequence of chemotherapy followed by concurrent chemoradiation therapy is an effective approach in patients with stage IIIA (N2-bulky) and IIIB (T4 N1-2 M0) NSCLC. The operation after induction chemoradiation therapy should be performed in carefully selected patients with surgically resectable diseases. The patients who achieved complete resection and with pathologic response of tumor can benefit from surgery following induction chemoradiation therapy.
Clinical Lung Cancer 09/2009; 10(5):353-9. · 2.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The development of resistance to chemotherapy is one of the major obstacles in the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP), and excision repair cross-complementing 1 (ERCC1) in NSCLC patients receiving cisplatin-based adjuvant chemotherapy (cisplatin plus vinorelbine or gemcitabine) after tumor resection. We used semiquantitative reverse-transcription polymerase chain reaction to detect the expression of MRP1, BCRP, LRP and ERCC1 mRNA in surgical resection specimens of 60 patients with stage IB through IIIA NSCLC. The expression level of each gene was analyzed in relation to clinicopathological factors, tumor-free survival (TFS), and overall survival. The results showed that stage IIIA (p=0.011), N1 and N2 status (p=0.008), high expression of MRP1 (p=0.034) and LRP (p=0.018) were associated with shorter TFS. Stage IIIA (p=0.0105), N1 and N2 status (p=0.009), high expression of MRP1 (p=0.021) and ERCC1 (p=0.012) were related to a shorter overall survival. Cox multivariate analyses revealed that early stage (p=0.013 and p=0.024), negative lymph node status (p=0.006 and p=0.011), and low MRP1 expression (p=0.022 and p=0.035) were independent predictors of favorable TFS and overall survival, respectively. Additionally, ERCC1 (p=0.019) was an independent predictor of favorable overall survival.
The International journal of biological markers 24(4):230-7. · 1.48 Impact Factor
