Gefitinib in the treatment of 41 cases with refractory non-small cell lung cancer

Objective： We observe the curative effect, median survival time, time to progression, quality of life and adverse effect of patients with advanced refractory non-small cell lung cancer （NSCLC） after gefitinib （Iressa） treatment. Methods： Forty-one patients with grade Ⅲb to Ⅳ NSCLC previously treated with two chemotherapy including 85.4% of patients after second line therapy were chosen. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or toxic reaction has become intolerable. The patients were required to receive tumor evaluation before the treatment, one month, two month and every three months after Iressa administration. Results： All of 41 patients were evaluable for therapeutic effect. Without complete regression being observed, partial response rate （PR）, stable disease （SD） and progression of disease （PD） were 43.9% （18/41）, 34.1% （14/41） and 22.1% （9/41）, respectively. The overall response rate was 43.9% （18141） and disease control rate （PR ＋ SD） was 78% （32/41）. The response rate in male was 42.1%, while it in female was 45.5% （P 〉 0.05）. Twenty-two of them （53.7%, 22/41） were still alive with 10.1 months of MST when the follow-up ended in November 2006. TTP and MST of patients who died was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% of all patients with 13 months of MST of PR patients. The Karnofsky enhanced 20 ＋ 5 after 28 days treatment without 3-4 degree of reactive toxicity. Conclusion： Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. Iressa is effective and safe for patients with poor performance status.     

Effects of weekly dose docetaxel monotherapy schedule for elderly patients with non-small cell lung cancer

Objective： To investigate the clinical efficacy and toxicity of weekly dose docetaxel monotherapy schedule in elderly with advanced non-small cell lung cancer （NSCLC）. Methods： 28 patients aged over 65 with advanced NSCLC were received with docetaxel （Aisu） 35 mg/m^2 on days 1, 8 and 15 every 28 days. A clinical evaluation on effectiveness, quality of life and toxicities was performed. Results： 28 patients were given 86 cycles＇ chemotherapy altogether. The overall response rate was 35.7% （10/28）. The clinical beneficial rate was 64.3% （18/28）. Mean KPS was increased from 75.5 at baseline to 87.7 after chemotherapy （P 〈 0.01）; lung cancer symptom scale （LCSS） scores of cough, hemoptysis, chest pain and dyspnea were increased from 64, 65, 62 and 65 to 90, 92, 87 and 88, respectively （P 〈 0.01）. The median time to progression （TTP） was 5.3 months; median survival time （MST） was 8.5 months. The main toxicities were fatigue, leukopenia and decrease of hemoglobin with well tolerance. Conclusion： Weekly dose docetaxel monotherapy schedule is a feasible, well-tolerated, and active scheme in the treatment of the elderly patients with advanced NSCLC.     

Vasculogenic mimicry in non-small cell lung cancer and its relationship with tumor stage

Objective： The purpose of the study was to study the mechanism of vasculogenic mimicry （VM） and its relationship with tumor stage in non-small cell lung cancer （NSCLC）. Methods： Forty-two patients with NSCLC were collected, 19 belonged to the early stage （stages Ⅰ ＋Ⅱ） while 23 were late stage （stages Ⅲ ＋ Ⅳ）. Moreover, 20 patients got surgical treat ment and 22 got chemotherapy. We studied the relationship of VM with stage, chemotherapeutic effect, HIF-la, microves sel density （MVD） and clinicopathologic features. Results： VM in patients of early stages were significantly more than late stages （68.4% vs 26.1%, P = 0.006）, and the positive rate of VM was proportional to HIF-la （P = 0.034）. But no correlation was found between VM and chemotherapeutic effect （14.3% vs 26.7%, P = 1.00） or MVD （P 〉 0.05）. Furthermore, we found VM also showed a negative correlation with distant metastases and lymph nodes metastases （P 〈 0.05） while no correlation was found with other clinicopathologic. Conclusion： VM was generated during the early stage in NSCLC and correlated with lymph nodes metastases. As the disease progressed, VM may be replaced by vascular endothelial cells, so the late-stage patients especially people with distant metastases had fewer VM. As the main factor produced by hypoxia, HIF-la may make a difference in VM formation. Thus we inferred VM might be a new target for targeted therapy, and could provide help for clinical staging and treatment.     

Relationship between hepatitis B virus infection and hepatic metastasis in non-small cell lung cancer

Objective： The purpose of the study was to explore the relationship between hepatitis B virus （HBV） infec tion and hepatic metastasis in non-small cell lung cancer （NSCLC）. Methods： Four hundred and eighty cases of NSCLC were retrospectively analyzed from January 2003 to January 2010, and the prevalence of hepatic metastasis of NSCLC in patients with and without hepatitis B virus infection were compared. Results： In the HBV carriers＇ group, the prevalence of synchronous hepatic metastasis and metachronous hepatic metastasis were 13.2% and 5.9%, respectively. Meanwhile in the non-HBV group, those were 21.6% and 9.5% respectively. A significant difference between the two groups was found （P 〈 0.05）. Conclusion： The prevalence of synchronous hepatic metastasis and metachronous hepatic metastasis in non-small cell lung cancer with HBV infection are lower than those in non-HBV infection group. Hepatic metastasis is infrequent in HBV infected cases of NSCLC.     

The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.     

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

Objective： To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer （NSCLC）. Methods： Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage Ilia and 14 patients with IIIb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine （600 mg/m^2） and cisplatin （20 mg/m^2）, once per week. Results： Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate （CR ＋ PR）, complete response rate （CR）, partially response rate （PR） were 83.3% （30/36）, 11.1% （4/36） and 72.2% （26/36） respectively. The median follow-up duration was 18.4 months. The 1- and 2-year overall survival rates were 77.8% （28/36） and 55.6% （20/36）, respectively. Conclusion： Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.     

Application of non-small cell lung cancer pleural effusion cell blocks in molecular pathological detection

Objective： The tumor tissues used in molecular pathological detection were usually obtain,ed by surgery, which would cause trauma and may not be suitable for the terminal cancer patients. This paper evaluated the value of the non-small cell lung cancer （NSCLC） pleural effusion cell blocks as tumor tissues replacement materials in the application of molecular pathological detection. Methods： Tumor cells were made into cell blocks through stratified centrifugal from 30 NSCLC pa- tients with the pleural effusion. The immunohistochemistry, fluorescence in situ hybridization （FISH） and gene sequencing methods were employed in our experiments. Results： The tumor cells of cell block section were rich and could keep part of histological structure. Immunohistochemistry staining could assist diagnosis and tumor parting. Epidermal growth factor receptor （EGFR） FISH-positive was found in 33.33% of the group, high polysomy in 6 cases, amplification in 4 cases. EGFR gene mutations were found in 8 cases of 30 samples, with an incidence of 26.67%, 6 cases were detected in the exon 19, and 2 cases were detected in the exon 21. Conclusion： The NSCLC pleural effusion cell blocks are useful for the diagnosis and determining the primary source of tumor, instructed targeted therapy.