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Tony S K Mok

Publications and source records attributed to Tony S K Mok.

At least 19 recordsLinked to original sources
PubMed2006

Increased thromboxane B(2) levels are associated with lipid peroxidation and Bcl-2 expression in human lung carcinoma.

There is little information regarding simultaneous investigations of thromboxane A(2) (TXA(2)) lipid peroxidation and Bcl-2, three cancer-related agents, and analyses of their relationships in lung cancer. The present study was to study thromboxane B(2) (TXB(2)), a stable metabolite of TXA(2), lipid peroxidation and Bcl-2 expression in 52 non-small cell lung carcinoma (NSCLC) tissue samples. The level of thiobarbituric acid reactive substances (TBARS), an index for lipid peroxidation was significantly increased in the lung tumor tissues, compared with non-tumor tissues. TXB(2) was much higher in the tumor tissues than non-tumor tissues. Interestingly, the concentration of TXB(2) in samples from those who smoked was higher than that from those who did not smoke. The expression of Bcl-2 was significantly elevated in the tumor tissues, compared to the non-tumor tissues. There was also a positive correlation between TXB(2) and TBARS in tumor tissues; advanced stage cancers had higher levels of TXB(2). This finding supports the idea that TXB(2) may have a role in promoting tumor growth. In conclusion, our study demonstrates that the production of TXB(2) is increased in lung tumor tissues and that such an increase can result in lipid peroxidation which may be met by an elevation in Bcl-2 expression.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Apoptosis induced by troglitazone is both peroxisome proliferator-activated receptor-gamma- and ERK-dependent in human non-small lung cancer cells.

The role of the peroxisome proliferator-activated receptor-gamma (PPARgamma) in cell differentiation, cell-cycle arrest, and apoptosis has attracted increasing attention. We have recently demonstrated that PPARgamma ligands-troglitazone (TGZ) induced apoptosis in lung cancer cells. In this report, we further studied the role of ERK1/2 in lung cancer cells treated by TGZ. The result demonstrated that TGZ induced PPARgamma and ERK1/2 accumulation in the nucleus, in which the co-localization of both proteins was found. The activation of ERK1/2 resulted in apoptosis via a mitochondrial pathway. Both PPARgamma siRNA and U0126, a specific inhibitor of ERK1/2, were able to block these effects of TGZ, suggesting that apoptosis induced by TGZ was PPARgamma and ERK1/2 dependent. Inhibition of ERK1/2 by U0126 also led to a significant decrease in the level of PPARgamma, indicating a positive cross-talk between PPARgamma and ERK1/2 or an auto-regulatory feedback mechanism to amplify the effect of ERK1/2 on cell growth arrest and apoptosis. In addition to ERK1/2, TGZ also activated Akt. Interestingly, inhibition of ERK1/2 prevented the activation of Akt whereas the suppression of Akt had no effect on ERK1/2, suggesting that Akt was not necessary for TGZ-PPARgamma-ERK pathway. However, the inhibition of Akt promoted the release of cytochrome c, suggesting the activation of Akt may have a negative effect on apoptosis induced by TGZ. In conclusion, our study has demonstrated that TGZ, a synthetic PPARgamma ligand, induced apoptosis in NCI-H23 lung cancer cells via a mitochondrial pathway and this pathway was PPARgamma and ERK1/2 dependent.

Apoptosis↗
PubMed2005

Correlation and prognostic significance of beta-galactoside alpha-2,6-sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular carcinoma.

AIM: To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS: Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS: The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage (r = -0.53, P = 0.019). Both decreased tumor ST6Gal I activity and increased serum msAFP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity (P = 0.028), increased serum msAFP percentage (P = 0.034) and poor tumor cell differentiation (P = 0.031) were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage (P = 0.022) and tumor cell differentiation status (P = 0.048) were independent prognostic indicators for patient overall survival. CONCLUSION: Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC.

Antigens, CD↗
PubMed2005

Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and a crucial regulator of cellular differentiation. PPAR-gamma ligands have been demonstrated to inhibit growth of several cancer cells. In this study, two human lung cancer cells (NCI-H23 and CRL-2066) and one human lung normal cell (CRL-202) were used for the experiments. The results showed that in consistence with the loss of viability, troglitazone (TGZ) induced apoptosis of CRL-2066 and NCI-H23 cells but not CCL-202 cells. TGZ upregulated PPAR-gamma expression in all the three lung cell lines, especially in the cancer cells. In association of the time-dependent inhibition of the cell proliferation, TGZ downregulated the expression of Bcl-w and Bcl-2 but activated extracellular signal-regulated kinase (ERK)1/2 and p38, suggesting that the growth-inhibitory effect of TGZ is associated with the reduction of Bcl-w and Bcl-2 and the increase of ERK1/2 and p38 activation. SAPK/JNK activation assay showed a decreased activity in all the three cell lines tested after TGZ treatment. It was also demonstrated that TGZ could activate PPAR-gamma transcriptionally. We conclude that TGZ inhibits growth of human lung cancer cells via the induction of apoptosis and the inhibition of cell growth, at least in part, in a PPAR-gamma-relevant manner. The mechanism of TGZ is associated with the activation of ERK and p38, the reduction of SAPK/JNK activity, and the alteration of Bcl-w and Bcl-2.

Apoptosis↗
PubMed2005

An intensive surveillance program detected a high incidence of hepatocellular carcinoma among hepatitis B virus carriers with abnormal alpha-fetoprotein levels or abdominal ultrasonography results.

PURPOSE: To study the incidence and treatment outcomes of hepatocellular carcinoma (HCC) detected in an intensive surveillance program (ISP) of hepatitis B virus (HBV) carriers. PATIENTS AND METHODS: We screened 1,018 HBV carriers by serum alpha-fetoprotein (AFP) measurement and abdominal ultrasonography (AUS). Patients with an abnormal AFP level or AUS result were enrolled in an ISP that included Lipiodol computed tomography followed by AFP measurement/AUS every 3 months for 2 years and then every 6 months thereafter. The rest were on routine surveillance for 2 years. RESULTS: A total of 9,849 serum AFP measurements and 3,053 AUSs were performed. After a median follow-up of 4.12 years, we diagnosed 24 HCCs among 78 patients with abnormal screening test results at enrollment (group A); 23 HCCs among 93 patients with only abnormal surveillance test results during follow-up (group B); and nine HCCs among 847 patients with 2 years of normal surveillance (group C). Annual incidence of HCC in the ISP was 760.2 (95% CI, 538.4 to 1,073.7) per 100,000. Mean tumor sizes were 3.02, 2.91, and 4.82 cm in groups A, B, and C, respectively (P = .01). Tumor resection rate of the ISP was 36.2%, although another 29.8% of the patients were eligible for locoregional ablative therapy. CONCLUSION: This study illustrated that a high incidence of relatively small HCCs may be detected by using intensive surveillance of high-risk HBV carriers. However, the surgical resection rate was low, and we were not able to demonstrate clinical benefit with the early detection. Future surveillance studies should consider incorporation of therapy aimed at long-term control of small-sized tumors.

Abdomen↗
PubMed2005

Phase II randomized study comparing the toxicity profile of gemcitabine plus cisplatin with gemcitabine plus oral etoposide in the treatment of advanced non-small cell lung cancer.

OBJECTIVE: This is a randomized phase II study designed to compare the toxicity profile of a non-platinum-based with a platinum-based regimen in the treatment of advanced non-small cell lung cancer. METHODS: Eighty-nine chemotherapy-naïve patients were randomized either to gemcitabine (1,000 mg/m2, 30-min infusion on days 1, 8 and 15) and oral etoposide (50 mg, days 1-14; GE group) or gemcitabine at the same schedule and cisplatin (75 mg/m2 on day 15; GP group). The primary endpoint is toxicity, and secondary endpoints include response rate, survival outcome and quality of life (QOL). RESULTS: The incidence of WHO grade 3 or 4 anemia, neutropenia and thrombocytopenia was 29, 44 and 22% (GE group), and 28, 49 and 23% (GP group), respectively (p = 0.75, 0.95 and 0.87, respectively). The rate of grade 2 or above nausea was numerically higher in the GP arm, but the difference was not statistically significant (GE 15.5%, GP 27.7%, p = 0.20). The rate of vomiting in the GE and GP arms was 20.0 and 20.5%, respectively (p = 0.96). However, subjective changes in QOL scores on nausea and vomiting were significantly higher in the GP arm (p = 0.001). Other symptoms including sore mouth and hair loss were significantly higher in the GE arm (p = 0.003 and 0.007, respectively). There were also significant differences observed in emotional (p = 0.014), cognitive (p = 0.028) and social functioning (p = 0.034) in favor of GP. The differences in tumor response (35.5 and 46.5% for GE and GP, respectively) were not significantly different. Median time to disease progression (33.8 and 40.7 weeks, respectively) and overall survival (41.4 and 57.3 weeks, respectively) were of borderline significance in favor of the GP arm (p = 0.055). CONCLUSION: This toxicity profile of GE is similar to GP, but the apparent inferior efficacy may discourage further investigation.

Adenocarcinoma↗
PubMed2005

Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.

This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.

Adult↗
PubMed2005

Prevention of hepatitis B virus reactivation in patients with nasopharyngeal carcinoma with lamivudine.

PURPOSE: Although the mainstay of treatment of patients with nasopharyngeal carcinoma (NPC) had been radiotherapy, chemotherapy has increasingly been adopted in conjunction with radiation and in advanced disease. In parts of Asia where NPC is prevalent, it is also known that around 10% of the population has chronic hepatitis B virus (HBV) infection. Cancer patients who are HBV carriers are frequently complicated by HBV reactivation during chemotherapy. This may result in liver damage, which disrupts anticancer therapy and compromises the patients' prognosis. In its most severe form, fatal hepatic failure may occur. With the increasing use of chemotherapy in NPC, the occurrence of HBV reactivation is likely to increase further. Although recent reports have suggested that the antiviral agent lamivudine may reduce HBV reactivation and its associated morbidity, there has been no data on this aspect in NPC patients. This study assessed the role of lamivudine in preventing HBV reactivation and its associated morbidity in NPC patients who have chronic HBV infection and are undergoing chemotherapy. MATERIALS AND METHODS: Two groups were studied. One group consisted of 16 patients who received prophylactic lamivudine prior to and until 8 weeks after discontinuing chemotherapy. The other comprised 21 historical control subjects who underwent chemotherapy without prophylactic lamivudine. The outcomes were compared. RESULTS: With prophylactic lamivudine, there were significantly fewer incidences of hepatitis (6.7% vs 33.3%, P = 0.047) and HBV reactivation (0% vs 28.6%, P = 0.027), and less disruption of chemotherapy (18.8% vs 67.7%, P = 0.045). CONCLUSION: Prophylactic lamivudine significantly reduces the incidence and morbidity of HBV reactivation in NPC patients undergoing chemotherapy.

Adult↗
PubMed2004

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.

PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

Adult↗
PubMed2004

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.

Adult↗
PubMed2004

Methodology for quality-of-life assessment: a critical appraisal.

The methodology for QOL assessment covers a wide range of topics. It involves a proper choice of instruments with appropriate psychometric properties, the administration of these instruments, frequency of measurements, missing data problems, and the method of analysis. There are currently debates on the meaning and interpretation of the HRQOL domains taking the form of arguing how to define minimal clinically meaningful difference and whether this can be used in regulatory approval for drug development. From a practical point of view, the authors proposed that a disease-specific checklist or symptom domains incorporated within a HRQOL questionnaire may be a middle ground to gain general agreements among academic institutions, manufacturers, and regulatory agencies to use a specific symptom checklist or domain as the primary end point for clinical trials together with other HRQOL domains as ancillary data for the study. Antiemetic trial with HRQOL assessments is an example. Most would agree, however, that no matter what HRQOL domains or symptoms are being studied, it should be based on a patient self-administered questionnaire as shown by the lack of sensitivity in the example in this article. Missing data are a problem in the data collection and handling. The authors have examined a few commonly used approaches and performed simulation to study their properties. The subscale-mean method when one has more than 50% of the information on a subscale generally reflects the true values. In practice, one still would have missing data that cannot be handled completely by imputation. The method of analysis must be flexible enough to incorporate the nature of these data. Two approaches have been discussed, and they are both flexible in terms of using all available information being obtained in a longitudinal fashion with variable visiting schedules and potential missing data. The HRQOL response variable approach is simple and easy to understand. The growth curve models approach provides more detailed information on average trends between treatment arms. In general, these two methods agree on the results of the example. They can be used to report clinical trial results using HRQOL data as end points.

Health Status↗
PubMed2004

A phase I safety and pharmacokinetic study of OGT 719 in patients with liver cancer.

OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000 mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity), area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.

Aged↗
PubMed2004

Brain metastasis responding to gefitinib alone.

A woman with stage IIIb non-small cell lung cancer (NSCLC) developed disease progression with brain metastases during chemotherapy. Due to unusual circumstances, the patient received gefitinib alone, without the use of corticosteroid treatment or radiotherapy. There was a dramatic clinical improvement within 1 week. Follow-up magnetic resonance imaging of the brain 1 month later showed decreases in both the size and number of brain metastases. The patient remains well 9 months after initiation of gefitinib. It is proposed that gefitinib may have a role in treatment of brain metastases from NSCLC.

Antineoplastic Agents↗
PubMed2004

False-negative rate of abdominal sonography for detecting hepatocellular carcinoma in patients with hepatitis B and elevated serum alpha-fetoprotein levels.

OBJECTIVE: Routine screening for hepatocellular carcinoma among chronic carriers of hepatitis B virus using a combination of abdominal sonography and serum alpha-fetoprotein levels is widely practiced. Negative results on an abdominal sonogram generally indicate the absence of hepatocellular carcinoma despite the elevation of alpha-fetoprotein levels, but the false-negative rate of abdominal sonography has not been established prospectively. SUBJECTS AND METHODS: In our screening program, we routinely investigated patients with Lipiodol (iodized oil) CT when they presented with alpha-fetoprotein levels above 20 ng/mL or a focal lesion as depicted on abdominal sonography. Lipiodol CT comprised a hepatic angiogram with injection of Lipiodol selectively in the hepatic arteries, followed by an unenhanced CT scan 10 days later. Positive findings on Lipiodol CT were confirmed histologically by biopsy or surgical resection. We defined false-negative as histologic diagnosis of hepatocellular carcinoma within 3 months of normal findings on screening abdominal sonography. RESULTS: One hundred three patients with elevated alpha-fetoprotein levels were investigated with Lipiodol CT within 2 months of abdominal sonography. Of these, three of 70 patients with negative abdominal sonography had histologically confirmed hepatocellular carcinoma. Thus, abdominal sonography has a false-negative rate of 4.3%. Lipiodol CT is associated with a significant false-positive rate of 43.7%. The sensitivity, specificity, and positive predictive value of abdominal sonography for early detection of hepatocellular carcinoma among hepatitis B virus carriers with elevated alpha-fetoprotein levels was 85.7%, 81.7%, and 54.5%, respectively. CONCLUSION: Negative results on a screening abdominal sonogram among hepatitis B virus carriers with elevated alpha-fetoprotein levels does not rule out the presence of small hepatocellular carcinoma. Routine use of Lipiodol CT as a supplementary screening tool is not recommended.

Adult↗
PubMed2003

Imatinib (STI-571) heals a gastrocutaneous fistula resulting from a malignant gastric stromal tumor.

The management of inoperable giant malignant gastrointestinal stromal tumor (GIST) of the stomach sed to be a formidable task. We report our success with the use of STI-571 in treating a patient with huge GIST of the stomach complicated by gastrocutaneous fistula after an unsuccessful laparotomy. The patient was a 49-year-old man who presented to our center with a painful epigastric mass in December 2001. Endoscopy, biopsy, and magnetic resonance scan confirmed that it was a malignant stromal tumor arising from the gastric fundus. Laparotomy with an intention to resect the tumor was performed in view of the obstructing symptoms. However, massive bleeding was encountered during dissection of the tumor and gastrectomy was abandoned. The case was further complicated with the development of a gastrocutaneous fistula in the early postoperative period. The patient ws then managed with naso-duodenal tube feeding and enteral STI-571 was prescribed. The fistula healed up in 20 days and the mass became impalpable 1 month afterwards. Follow-up computed tonography (CT) scan 3 months later confirmed significant tumor reduction, and the patient has experienced no side effects from the treatment

Benzamides↗
PubMed2003

A prospective study of pre-treatment cell kinetics and clinical outcome in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To study pre-treatment cell kinetics and their clinical correlations in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Ninety newly diagnosed NPC patients were studied using in vivo Bromodeoxyuridine (BrdU) labeling and flow cytometric analysis. Immunohistochemical staining for BrdU and Ki 67 was also performed. RESULTS: The median S-phase duration (Ts) was 6.2 h (range 3.5-18.7 h), median flow cytometric labeling index (FCM-LI) was 7.4% (1.3-37.6%), and median potential doubling time (Tpot) was 3.6 days (0.5-19.9 days). The median histologic labeling index (H-LI) was 12.4% (1.2-43.3%), and median histologic Tpot (H-Tpot) was 2.1 days (0.5-33.3 days). FCM-LI and H-LI were both positively correlated with Ki67 whereas Tpot and H-Tpot were both negatively correlated with Ki67 and N-stage. In univariate analysis, Tpot and H-Tpot showed a trend for progression free survival. Tpot was significantly associated with local relapse free survival, but lost its significance in multivariate analysis. N-stage was the only significant prognostic factor for all radiotherapy outcomes in both univariate and multivariate analyses. CONCLUSIONS: Tpot was the only pre-treatment cell kinetic parameter for which some evidence was found for an association with survival in NPC patients. Future studies should aim to combine cell kinetic parameters together with other biological markers and clinical parameters to provide more useful prognostic information to guide individual patient's therapy.

Adult↗