Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. MATERIALS AND METHODS: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively. RESULTS: In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity. CONCLUSION: These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.

Absorption of irrigation fluid occurs during 1470 nm diode laser vaporization of the prostate / 中国内镜杂志

Objective To investigate and evaluate the effects and safety of the operationabsorption of irrigation fluid occurs during 1470 nm diode laser vaporization of the prostate by ethano. Methods We retrospectively analyzed the clinical data about 32 cases of BPH treated by 1470 nm diode laser vaporization from May 2016 to December 2016 intraoperative use of isotonic saline contains 1.0％ ethanol as perfusion fluid, monitor the patients' breath ethanol concentration, calculation of perfusion fluid absorption. Results All the operations were successfully completed, the average operation time was (57.6 ± 32.9) min, the average perfusion fluid volume was (21.5 ± 9.9) L, only 5 cases detected perfusion fluid absorption, the average absorptive amount was (156.8 ± 111.7) ml. During operation, all the patients with stable breathing, circulation, no alcohol poisoning symptoms, no bleeding, capsular perforation, cardiorespiratory failure occurred. All the 32 cases patients were followed up for 3 months, which revealed a significant improvement in dysuresia, no severe complications such as urethrostenosis, urinary incontinence, secondary hemorrhage were noted. Conclusion Fluid absorption little occurs during 1470 nm diode laser vaporization, it is safe and effective in treatment of benign prostatic hyperplasia.

Establishment of a Novel Method for Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Mutations in Lung Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.</p><p><b>METHODS</b>A review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility.</p><p><b>RESULTS</b>Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform.</p><p><b>CONCLUSIONS</b>We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.</p>

Insight into early-phase trials for lung cancer in the United States / 癌症

<p><b>INTRODUCTION</b>Few data have been published comparing early-phase trials for lung cancer between China and the United States (US). This study was to investigate the differences of phase 1 trials for lung cancer between these two countries.</p><p><b>METHODS</b>In 2014, a cross-sectional survey was conducted to compare phase 1 trials for lung cancer between the Guangdong Lung Cancer Institute (GLCI), the University of Wisconsin Carbone Cancer Center (UWCCC), and the University of Texas MD Anderson Cancer Center (MDACC).</p><p><b>RESULTS</b>We found that the GLCI had a lower percentage of phase 1 lung cancer trials than the MDACC in December 2014 (23.8% [5/21] vs. 59.8% [28/47], P = 0.006) and the UWCCC in September 2014 (16.7% [3/18] vs. 34.8% [8/23], P = 0.345). Descriptive analyses were performed for early-phase trials conducted by the Cancer Therapy Evaluation Program at the National Cancer Institute (CTEP/NCI), the MDACC, and the Chinese Thoracic Oncology Group (CTONG). There were 149 ongoing early-phase trials in the Department of Investigational Cancer Therapeutics (Phase 1 program) at the MDACC in October 2014. In contrast, no phase 1 trials had been initiated by the CTONG since its establishment in 2007.</p><p><b>CONCLUSIONS</b>These data suggest that a significantly higher percentage of phase 1 trials for lung cancer were conducted in the US than in China. Early-phase oncology trials with robust preclinical data had a higher chance of being approved by the Investigational Drug Branch at the CTEP/NCI. Given the importance of early-phase oncology trials in developing innovative cancer medicines, such studies should be highly encouraged and strategically funded in China.</p>

Detecting the spectrum of multigene mutations in non-small cell lung cancer by Snapshot assay / 癌症

As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer (NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor (EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog (KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen activated protein kinase kinase 1 (MEK1), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51 (46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively (P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100% (positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.

Survival without common toxicity criteria grade 3/4 toxicity following second-line treatment with pemetrexed for nonsquamous non-small cell lung cancer in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy of pemetrexed in the second-line treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) has been shown to be similar to that of docetaxel in a recent study; additionally, pemetrexed was associated with much better safety and toxicity profiles. Here, the survival without common toxicity criteria grade 3/4 toxicity (SWT) data from a post hoc analysis of this recent prospective NSCLC study in Chinese patients is reported. This post hoc analysis differs from the main study; it focuses on the nonsquamous population to align with the current approval for pemetrexed in China.</p><p><b>METHODS</b>A total of 154 patients with nonsquamous NSCLC received either pemetrexed (500 mg/m(2) intravenously (IV)) or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. SWT was analyzed using Kaplan-Meier and univariate Cox methods.</p><p><b>RESULTS</b>Patients treated with pemetrexed had a longer median SWT than patients treated with docetaxel (7.4 months versus 1.2 months; unadjusted hazard ratio = 0.59, 95% confidence interval (CI): 0.41-0.84; P = 0.003). At 12 and 18 months, the SWT event-free probability for pemetrexed patients (18 months: 24.5%, 95%CI 13.9%-36.6%, vs. 12.3%, 95% CI 4.8%-23.6%) was greater than that for docexatel patients (12 months: 37.3%, 95% CI 26.5%-48.0%, vs. 23.3%, 95% CI 14.4-33.4). The progression-free survival without common toxicity criteria grade 3/4 toxicity (PFS-WT) was also statistically significantly longer for patients treated with pemetrexed than patients treated with docetaxel (1.9 months vs. 1.1 months, P = 0.002).</p><p><b>CONCLUSIONS</b>Chinese patients with nonsquamous NSCLC disease treated with pemetrexed had improved SWT beyond 6 months than those receiving docetaxel. This analysis supports a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of Chinese nonsquamous NSCLC patients.</p>

Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib / 中华医学杂志(英文版)

The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments. There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months. The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy, so it was suspected that the leukoencephalopathy was associated with gefitinib.

Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidermal growth factor receptor (EGFR) mutations in lung carcinomas can make the disease more responsive to the treatment with tyrosine kinase inhibitors. We aimed to evaluate the prevalence of EGFR mutations in a large series of lung carcinomas.</p><p><b>METHODS</b>We examined 1195 consecutive lung cancer patients for EGFR mutations in exons 18, 19, and 21 using direct sequencing of polymerase chain reaction products. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > 1 year ago), or current smokers (quit < 1 year ago).</p><p><b>RESULTS</b>There were EGFR mutations in 9 (4.5%) of 201 squamous carcinomas, in 1 (2%) of 50 large cell carcinomas, and in 1 (2.3%) of 44 small cell carcinomas that were investigated. Three hundred and twenty-seven mutations were found in the series of 858 adenocarcinomas (38.1%). Among 858 lung adenocarcinomas, we detected EGFR mutations in 250 (48.6%) of 514 never smokers, 39 (33.9%) of 115 former smokers, and 38 (16.6%) of 229 current smokers. Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P = 0.0002) or stopped smoking less than 15 years ago (P = 0.033) compared with individuals who never smoked.</p><p><b>CONCLUSIONS</b>Adenocarcinoma is the most frequent EGFR mutation pathologic type in lung cancer. The likelihood of EGFR mutations in exons 18, 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 15 years ago. These data can assist clinicians in assessing the likelihood of exons 18, 19, or 21 EGFR mutations in Chinese patients with lung cancer when mutational analysis is not feasible.</p>

Efficacy and safety of gefitinib or docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had failed previous platinum-based first-line chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of gefitinib or docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had failed previous platinum-based first-line chemotherapy.</p><p><b>METHODS</b>We retrospectively reviewed 222 Chinese NSCLC patients in the subgroup of INTEREST (gefitinib versus docetaxel in previously treated non-small cell lung cancer) study. Survival analysis was evaluated by Kaplan-Meier method, and Functional Assessment of Cancer Therapy-Lung (FACT-L) was used to compare the quality of life between gefitinib group and docetaxel group.</p><p><b>RESULTS</b>A total of 222 patients were analyzed in this subgroup study. 107 patients were treated with gefitinib, and 115 patients treated with docetaxel. There were all balanced between the two groups in terms of sex, age, staging and pathology in patient characteristics. The median overall survival in the two groups was similar (11 months in the gefitinib group vs. 14.0 months in the docetaxel group, P = 0.783). The progression-free survival (PFS) was also similar between the two groups (median PFS: 3.4 months in gefitinib group vs. 3.8 months in docetaxel group, P = 0.214). The response rate in gefitinib group was significantly higher than that in the docetaxel group (21.9% vs. 9.1%, P = 0.016).</p><p><b>CONCLUSION</b>The efficacy of gefitinib is similar with that of docetaxel in pretreated patients with locally advanced or metastatic NSCLC, however, gefitinib is more favorable in the tolerance and quality of life improvement.</p>

A diagnostic model of cerebrospinal protein fingerprint pattern for brain metastases of non-small cell lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a diagnostic model of protein fingerprint pattern in the cerebrospinal fluid (CSF) for non-small-cell lung cancer (NSCLC) patients with brain metastases.</p><p><b>METHODS</b>The CSF samples were obtained from 29 NSCLC patients with brain metastasis, 23 non-tumor patients and 10 early-stage NSCLC patients without brain metastases for analysis of the protein expression profiles using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data were then analyzed by Biomarker Wizard software, and the tree analysis patterns were generated using the decision-tree model in Biomarker Patterns software. The diagnostic model was tested for its clinical application.</p><p><b>RESULTS</b>Five protein peaks were identified showing differential expression between patients with brain metastases and those without brain metastases. Combination of the 3 protein peaks (m/z: 8698.00, 1215.32 and 1245.70) could discriminate these two samples with a sensitivity of 100.00% (29/29) and a specificity of 100.00% (23/23). Five proteins were differentially expressed between the NSCLC patients with brain metastases and the non-tumor patients. With one protein peak (m/z: 6050.00), these two samples could be discriminated with a sensitivity of 90.00% (9/10) and a specificity of 78.26% (18/23).</p><p><b>CONCLUSION</b>The established diagnostic model of CSF protein fingerprint pattern provides high sensitivity and specificity in the diagnosis of NSCLC with brain metastasis.</p>

Efficacy and safety of Erlotinib in the treatment for advanced non-small cell lung cancer in Chinese patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the efficacy and the adverse effects of erlotinib in the treatment for advanced non-small cell lung cancer (NSCLC) in Chinese patients.</p><p><b>METHODS</b>From November 2005 to March 2009, a total of 519 patients with unresectable, local advanced, relapsed or metastatic NSCLC were enrolled in the trial. All the patients were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity or for other reasons. The response rate, time to disease progression, overall survival and toxicity were analyzed.</p><p><b>RESULTS</b>Of these 519 patients, 1 case had complete response, 127 cases had partial response and 263 cases had stable disease, resulting in an overall response rate (CR + PR) of 26.7%, disease stable rate of 54.9% and disease control rate (CR + PR + SD) of 81.6%. The median time to progression was 6.44 months and median overall survival was 15.37 months. The major erlotinib treatment-related adverse events (AE) were mild (CTC AE 1/2), only 3 cases had severe adverse effect, 1 case had interstitial lung disease and died of respiratory failure.</p><p><b>CONCLUSION</b>The study presents excellent response rates, time to progression and overall survival of erlotinib treatment for advanced NSCLC in Chinese patients, and its adverse events are tolerable.</p>

Proteinchip-flight mass spectrometry for screening differentially expressed proteins in the serum of cervical cancer patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the differentially expressed proteins in the serum of patients with cervical cancer for use as the biomarkers for early diagnosis of cervical cancer.</p><p><b>METHODS</b>Surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) with weak cationic chips (CM10) was used to examine the serum samples of 24 patients with cervical squamous cell carcinoma and 25 age-matched healthy women. The protein fingerprints were obtained, and bioinformatic analysis was performed to identify the differentially expressed proteins in the serum of the patients.</p><p><b>RESULTS</b>Fifty-two differentially expressed proteins were detected in the serum of cervical cancer patients (P<10(-5)), among which 6 proteins with mass/charge ratio of 4173.77, 5903.09, 6087.12, 10716.9, 6109.61 and 3397.41, respectively, showed lowered expression in the serum of cervical cancer patients. Two diagnostic models for cervical cancer were generated using software, including one consisting of the 4173.77(M/Z) protein with the diagnostic specificity of 96% and sensitivity of 75% for cervical cancer and the other consisting of 3 proteins at 5335.81(M/Z), 7562.99(M/Z), and 9287.89(M/Z) with specificity of 91.67% and sensitivity of 96.0%.</p><p><b>CONCLUSION</b>Cervical cancer patients show different serum protein expression profile from healthy women. The 6 differential proteins identified may serve as specific serum biomarkers in close relation to the origin and progression of cervical cancer.</p>

Surgical treatment of ipsilateral multi-focal non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVES</b>The staging and treatment of multi-focal non-small cell lung cancer (NSCLC) are controversial. This study evaluated the effectiveness of surgical treatment for the ipsilateral multi-focal NSCLC.</p><p><b>METHODS</b>Sixty-eight patients with multi-focal NSCLC underwent complete resection from December 1999 to December 2006. This series included 44 males and 24 females, with a mean age of 60.3 years old (range from 33 to 81 years old). Fifty-four patients had multiple nodules in primary lobe (T4) and 13 patients had additional nodules in non-primary lobe (M1), and a patient was proved to have synchronous primary NSCLC lesions. Surgical treatments included lobectomy in 53 cases, bilobectomy in 4 cases, pneumonectomy in 2 cases, and lobectomy combined with wedge resection in 9 cases.</p><p><b>RESULTS</b>The median overall survival time of this series was 30 months. Prognostic study demonstrated that mediastinal lymph node metastasis and bronchioloalveolar carcinoma histology had significant impact on overall survival. The median survival times were 39 months for patients with N0 and N1, and 14 months for patients with N2, respectively, and there was significant difference between the groups (P < 0.01). The difference in survival was significant between patients with bronchioloalveolar carcinoma components and other NSCLC histologic types (P < 0.01), and the median survival times were 46 months and 20 months, respectively.</p><p><b>CONCLUSION</b>Surgery could provide choice for multi-focal NSCLC patients (T4 and M1), especially for patients with bronchioloalveolar carcinoma components and without mediastinal lymph node metastasis.</p>

Surgical treatment for bronchioloalveolar carcinoma with ipsilateral intrapulmonary metastatic nodules / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The staging and treatment of bronchioloalveolar carcinoma (BAC) with pulmonary metastasis are still controversial. This study aimed at evaluating the current staging of BAC with ipsilateral intrapulmonary metastatic nodules and the therapeutic effectiveness of surgical resection.</p><p><b>METHODS</b>The clinicopathological data of 729 completely and surgically resected patients with non-small cell lung cancer (NSCLC) from December 1999 to December 2006 were retrospectively reviewed. Prognostic factors affecting the overall survival were analyzed by the Kaplan-Meier method and compared by the log rank test.</p><p><b>RESULTS</b>Among 67 NSCLC patients with ipsilateral intrapulmonary metastatic nodules, 54 had multiple nodules in the lobe with primary lesion (T4, PM1) and 13 had additional nodules in the other ipsilateral lobes (M1, PM2). This series consisted of 40 males and 27 females, with a median age of 60.0 years. Of those, 28 had the lesions containing pure or some bronchioloalveolar carcinoma component, while the other 39 had a NSCLC lesions containing non-bronchioloalveolar carcinoma components. The median overall survival time of this series was 24.0 months. Prognostic study demonstrated that bronchioloalveolar carcinoma histology and mediastinal lymph node metastasis had significant adverse impact on the overall survival. The median survival time of the patients with bronchioloalveolar carcinoma was 58.0 months versus 27.0 months in patients with other subtypes of NSCLC (P < 0.01). The median survival times were 39.0 months for the patients with N0 or N1 versus 14.0 months for patients with N2, with a significant difference between the two groups (P < 0.01). There was no significant difference in the survival time between the patients with PM1 (36 months) and those with PM2 (24 months) (P > 0.05).</p><p><b>CONCLUSION</b>Surgical resection is effective for NSCLC patients with ipsilateral intra-pulmonary metastasis, especially for those with bronchioloalveolar carcinoma components. Our results suggest that the current TNM classification system may be inappropriate for the NSCLC patients with ipsilateral intrapulmonary metastatic nodules, and may need a modification.</p>

Update of gene therapy for aging-related erectile dysfunction / 中华男科学杂志

The incidence of erectile dysfunction (ED) rises with the increase of age, for which gene therapy is a new option in the recent years. Different target genes, vehicles and therapeutic strategies have been tried and yielded good results. This paper offers an overview of the current advances in gene therapy for aging-related ED.

Association of XAGE-1b gene expression with clinical characteristics of non-small cell lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the association between XAGE-1b gene expression and the clinical characteristics of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Tumor tissue and adjacent normal lung tissue specimens were obtained surgically from 30 patients with resectable NSCLC, from which the total RNA was extracted for RT-PCR to amplify full-length XAGE-1b gene. The products of RT-PCR were identified by electrophoresis and sequencing. The expression of XAGE-1b gene and its association with the clinical characteristics of the patients were analyzed.</p><p><b>RESULTS</b>In the 30 tumor tissue specimens, the expression rate of XAGE-1b gene was 40%, but none of the normal lung tissues expressed this gene. The gene expression was not related to the patients' age, gender, tumor differentiation or clinical stages, but showed significant correlation to their pathological classification. The expression rate of XAGE-1b gene in adenocarcinoma was much higher than that in tumors of other pathological types (61.1% vs 8.3%, P=0.015). XAGE-1b gene expression tended to increase with the TNM stages, which, however, failed to find statistical data support (P>0.05).</p><p><b>CONCLUSIONS</b>XAGE-1b gene is highly expressed in lung adenocarcinoma, and can be an ideal target for tumor immunotherapy.</p>

Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer: phase I trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a potent radiosensitizer such as gemcitabine, which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT.</p><p><b>METHODS</b>Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks). Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m(2), escalated by 100 mg/m(2) increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached.</p><p><b>RESULTS</b>A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m(2) (level 3) no neurology toxicity was observed. At 600 mg/m(2) two out of 9 patients developed grade 4 thrombocytopenia. One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700 mg/m(2) two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness.</p><p><b>CONCLUSIONS</b>The MTD was reached at a dose of 700 mg/m(2). The dose of 600 mg/m(2) would be considered for further study.</p>

Detection of micrometastasis in mediastinal lymph nodes in operable non-small cell lung cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Using the LUNX-mRNA as a marker and RT-PCR technique to assess mediastinal lymph nodes in patients with operable NSCLC, to evaluate at gene level the feasibility of this method in detection of micrometastasis in NSCLC and the necessity of systematic mediastinal lymphadenectomy during surgery.</p><p><b>METHODS</b>Twenty patients with operable NSCLC were involved in this study. The mediastinal lymph nodes were taken during operation. RT-PCR assay was carried out to detect the LUNX-mRNA. Ten cases with benign lung disease were assayed by the same method as control.</p><p><b>RESULTS</b>Seventy one mediastinal lymph nodes were obtained from 20 patients, 8 (11.3%) of which showed histologically metastasis with HE staining, while 23 (32.4%) were LUNX-mRNA positive by RT-PCR, P < 0.001. Micrometastasis was detected in 25.4% of all lymph nodes. LUNX-mRNA was found to be positive in 23.6% of lymph nodes from 15 patients with stage I A-II B NSCLC compared with 62.5% from 5 patients with stage III NSCLC, with a significant difference (P = 0.003).</p><p><b>CONCLUSION</b>About 25.4% of mediastinal lymph nodes are with micrometastasis in patients with operable NSCLC. Systematic mediastinal lymphadenectomy is necessary to deal with the regional lymph nodes during surgery.</p>

Transdermal fentanyl for the management of cancer pain: a survey of 4492 patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and adverse effects of transdermal fentanyl in management of patients with cancer pain.</p><p><b>METHODS</b>A total of 4492 patients (aged 3-90) with cancer pain were enrolled in this multicenter study. The mean age was 58.5 (3 approximately 90) years old. All patients received transdermal fentanyl. The patients were asked to record the attacks of pain, quality of life, and any side effects of the treatment.</p><p><b>RESULTS</b>Baseline mean pain intensity was 7.37. On days 1, 3, 6, 9, 15, and 30, the mean scores of pain were decreased to 4.04, 2.98, 2.52, 2.19, 1.85 and 1.61, respectively (P < 0.01). The effective rate was 96.8%. The mean doses of fentanyl were 32.37 microg/h (25-200 microg/h) on the initial day, 42.57 microg/h and 49.57 microg/h (25-225 microg/h) on days 15 and 30. The quality of life was significantly improved after treatment (P < 0.01). The common side effects were constipation (9.8%), nausea (13.6%), dizziness (6.5%), vomiting (3.9%), sedation (2.0%) and respiratory depression (0.2%). The incidence of constipation was related to age, and the incidence of vomiting and difficulty of urination was related to gender. The majority (84.5%) of patients preferred continuation of the treatment with transdermal fentanyl.</p><p><b>CONCLUSION</b>Transdermal fentanyl for the patients with cancer pain is effective, safe, convenient and can improve the quality of life. Transdermal fentanyl can be recommended as one of first-line drugs for the treatment of patients with moderate to severe cancer pain.</p>

Treatment of non-small-cell lung cancer with paraplatin given by two different dosage calculation methods / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the reasonable dosage for paraplatin according to different dosage calculations.</p><p><b>METHODS</b>A prospective, randomized, single-blinded study on 54 patients with advanced non-small-cell lung cancer (NSCLC) treated with paraplatin was conducted. Patients were divided to 2 groups. In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS). Hematological toxicity, response rate and survival rate in the two groups of patients were compared.</p><p><b>RESULTS</b>Neutropenia in group A and group B was seen in 77.8% and 37.0% (P < 0.05), and thrombocytopenia in 18.5% and 3.7% (P > 0.05) of patients, respectively. Hemoglobin decrease was seen in 48.2% of patients in both groups. The average quantity of paraplatin given in one cycle of treatment was 535.93 +/- 106.71 mg and 398.52 +/- 71.72 mg (P < 0.01) respectively. The average time interval between treatment cycles was 27.04 +/- 5.30 d and 22.85 +/- 2.80 d (P < 0.05). The response rate and survival rate of patients in group A and B were 22.2% versus 48.2% (P < 0.05), and 40.7% versus 44.4% (P > 0.05) respectively, but the median survival time was identical (12 months) in the two groups.</p><p><b>CONCLUSION</b>NSCLC patients given paraplatin with dosages calculated on the basis of AUC have higher response rate and less severe hematological toxicity than those given paraplatin with dosages on the basis of body surface. However, the median survival time and survival rate have no statistical differences between the two groups of patients.</p>