Biomedical subjects

Benny Zee

Publications and source records attributed to Benny Zee.

At least 19 recordsLinked to original sources

PubMed2006

Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma.

PURPOSE: To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared. RESULTS: Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease. CONCLUSION: Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.

Biomarkers, Tumor↗

PubMed2006

Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma.

PURPOSE: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that pEBV DNA reflects tumor burden and metabolic activity by evaluating its relationship with tumor volume and 18F-fluorodeoxyglucose (18F-FDG) uptake in NPC. METHODS AND MATERIALS: Pre-treatment pEBV DNA analysis, 18F-FDG positron emission tomography-computed tomography scan (PET-CT) and magnetic resonance imaging (MRI) of the head and neck were performed in 57 patients. Net volume (cm3) of the primary tumor (T(vol)) and regional nodes (N(vol)) were quantified on MRI. 18F-FDG uptake was expressed as the maximum standardized uptake value (SUV(max)) at the primary tumor (T(suv)) and regional nodes (N(suv)). Lesions with SUV(max) > or = 2.5 were considered malignant. Relationship between SUV(max), natural logarithm (log) of pEBV DNA, and square root (sq) of MRI volumes was analyzed using the Wilcoxon test. A linear regression model was constructed to test for any interaction between variables and disease stage. RESULTS: Log-pEBV DNA showed significant correlation with sq-T(vol) (r = 0.393), sq-N(vol) (r = 0.452), total tumor volume (sq-Total(vol) = T(vol) + N(vol), r = 0.554), T(suv) (r = 0.276), N(suv) (r = 0.434), and total SUV(max) (Total(suv) = T(suv) + N(suv), r = 0.457). Likewise, sq-T(vol) was correlated to T(suv) (r = 0.426), and sq-N(vol) with N(suv) (r = 0.651). Regression analysis showed that only log-pEBV DNA was significantly associated with sq-Total(vol) (p < 0.001; parameter estimate = 8.844; 95% confidence interval = 3.986-13.703), whereas Sq-T(vol) was significantly associated with T(suv) (p = 0.002; parameter estimate = 3.923; 95% confidence interval = 1.498-6.348). CONCLUSION: This study supports the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV-related NPC.

Adult↗

PubMed2006

Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial.

OBJECTIVE: To investigate the effects of compliance and periodic telephone counselling by a pharmacist on mortality in patients receiving polypharmacy. DESIGN: Two year randomised controlled trial. SETTING: Hospital medical clinic. PARTICIPANTS: 502 of 1011 patients receiving five or more drugs for chronic disease found to be non-compliant at the screening visit were invited for randomisation to either the telephone counselling group (n = 219) or control group (n = 223) at enrollment 12-16 weeks later. MAIN OUTCOME MEASURES: Primary outcome was all cause mortality in randomised patients. Associations between compliance and mortality in the entire cohort of 1011 patients were also examined. Patients were defined as compliant with a drug if they took 80-120% of the prescribed daily dose. To calculate a compliance score for the whole treatment regimen, the number of drugs that the patient was fully compliant with was divided by the total number of prescribed drugs and expressed as a percentage. Only patients who complied with all recommended drugs were considered compliant (100% score). RESULTS: 60 of the 502 eligible patients defaulted and only 442 patients were randomised. After two years, 31 (52%) of the defaulters had died, 38 (17%) of the control group had died, and 25 (11%) of the intervention group had died. After adjustment for confounders, telephone counselling was associated with a 41% reduction in the risk of death (relative risk 0.59, 95% confidence interval 0.35 to 0.97; P = 0.039). The number needed to treat to prevent one death at two years was 16. Other predictors included old age, living alone, rate of admission to hospital, compliance score, number of drugs for chronic disease, and non-treatment with lipid lowering drugs at screening visit. In the cohort of 1011 patients, the adjusted relative risk for death was 1.61 (1.05 to 2.48; P = 0.029) and 2.87 (1.80 to 2.57; P < 0.001) in patients with compliance scores of 34-66% and 0-33%, respectively, compared with those who had a compliance score of 67% or more. CONCLUSION: In patients receiving polypharmacy, poor compliance was associated with increased mortality. Periodic telephone counselling by a pharmacist improved compliance and reduced mortality. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register: SRCTN48076318.

Adult↗

PubMed2006

Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG).

BACKGROUND: The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer. PATIENTS AND METHODS: Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks. RESULTS: The median number of cycles delivered per patient was 2 (range 1-6). Two patients (9%) had >or= 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55-9.39). CONCLUSIONS: Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.

Adenocarcinoma↗

PubMed2006

Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: a study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG).

BACKGROUND AND PURPOSE: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. PATIENTS AND METHODS: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. RESULTS: On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. CONCLUSIONS: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.

Adult↗

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

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

A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma.

BACKGROUND: Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low (< 20%) and there is no convincing evidence for improved survival. Cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) used in combination, by contrast, has shown promise in a phase II study. We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial. METHODS: Patients with histologically confirmed unresectable HCC were randomly assigned to receive either doxorubicin or PIAF every 3 weeks, for up to six cycles. The primary endpoint was overall survival, and secondary endpoints were response rate and toxicity. Survival differences were calculated using the Kaplan-Meier method. Treatment groups were compared for differences in the incidence of adverse events using chi-square tests. All statistical tests were two-sided. RESULTS: The median survival of the doxorubicin and PIAF groups was 6.83 months (95% confidence [CI] = 4.80 to 9.56) and 8.67 months (95% CI = 6.36 to 12.00), respectively (P = 0.83). The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 (95% CI = 0.71 to 1.32). Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response. The overall response rates in the doxorubicin and PIAF groups were 10.5% (95% CI = 3.9% to 16.9%) and 20.9% (95% CI = 12.5% to 29.2%), respectively. Neutropenia, thrombocytopenia, and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin. CONCLUSION: Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor.

Adult↗

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

Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group.

BACKGROUND: The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS. METHODS: Between January 1996 and December 2000, 2915 patients received primary radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median follow-up of 3.1 years, 319 patients had developed local failure as the first failure, with or without synchronous regional/distant failure. OS was calculated from the start of primary RT. Univariate and multivariate analyses were performed to identify prognostic factors for OS in patients with isolated local failure. RESULTS: The T classification distribution of the local failure (rT classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3, and 77 (24%) rT4. The rT classification was the same as the initial T classification in 82% of patients. Two hundred seventy-five patients (86%) had isolated local failure, and 232 (84%) of them did not have any distant metastasis or regional failure develop during follow-up. Salvage treatment was given to 200 patients (73%) with isolated local failure. One hundred fifty-nine patients (80%) received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or without postoperative RT, and 19 patients (9%) were treated with chemotherapy alone. Four patients died of RT complications, and one died of chemotherapy toxicity in the absence of active NPC. The 3-year actuarial OS for patients with isolated local failure was 74%. On multivariate analysis, advanced initial T classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the subgroups of patients who had the same recurrent and initial T classification, salvage treatment was associated with improved OS only in the subgroup with T1 to T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48) or T4 (n = 54) disease. CONCLUSIONS: Most patients with first local failure have localized disease. Salvage treatment is feasible in most of the patients with clinically isolated local failure. Patients who had early initial T classification have a more favorable prognosis. Subgroup analysis suggests that salvage treatment only prolongs survival in patients with T1 to T2 recurrent disease.

Adult↗

PubMed2005

Analysis and interpretation of health-related quality-of-life data from clinical trials: basic approach of The National Cancer Institute of Canada Clinical Trials Group.

Clinicians are being confronted with increasing amounts of health-related quality of life (HRQOL) data. Thus, there is a need for a greater understanding of the analysis and interpretation of HRQOL so that the data can be reported in an appropriate manner. The approach of the Clinical Trials Group of the National Cancer Institute of Canada emphasises the clinical meaning of the results, while avoiding complex statistical modelling. It consists of four steps: calculating the questionnaire completion rates, calculating the baseline scores, determining the individual change in scores over time for the domains specified in the trial hypothesis, and culminates in determining the proportions of patients who have reported clinically meaningful changes in scores since baseline. A rationale supporting each step is given. This approach is presented as a simple and practical aid to the analysis, interpretation and reporting of HRQOL results.

Canada↗

PubMed2005

Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.

BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P = 0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values < 0.01). Field size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function.

Adolescent↗

PubMed2004

Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience.

PURPOSE: To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level. METHODS AND MATERIALS: Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively. CONCLUSION: Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.

Adult↗

PubMed2004

Quality of life in ovarian cancer patients: comparison of paclitaxel plus cisplatin, with cyclophosphamide plus cisplatin in a randomized study.

PURPOSE: Formal quality-of-life (QOL) assessments may contribute important information on patient symptoms. Despite many trials of systemic chemotherapy in ovarian cancer, reports of its effect on QOL are few. PATIENTS AND METHODS: QOL was assessed in an Intergroup randomized trial comparing paclitaxel plus cisplatin to cyclophosphamide plus cisplatin in women with advanced ovarian cancer. One hundred fifty-two eligible patients accrued in Canada completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a trial-specific checklist at baseline (after surgical debulking) and at regular intervals during and after chemotherapy. Mean change scores over time in the two arms were calculated. RESULTS: Compliance with QOL questionnaire completion was excellent (81% to 93%). In general, deterioration was seen in the QOL domains immediately after chemotherapy (day 8 of cycle 1), followed by clinically meaningful improvements compared with baseline (change scores > or = 10) in both arms during the treatment period in a number of domains and items, including global QOL, emotional function, social function, fatigue, pain, sleep, constipation, appetite, abdominal swelling, and abdominal cramps. Improvements in global QOL persisted for the duration of follow-up. More neurosensory effects and myalgia were documented in the paclitaxel arm; however, this did not adversely affect global or other domains of QOL and improved once chemotherapy was completed. CONCLUSION: Improvement from baseline in QOL measures was seen in both treatment arms. The greater neurologic and muscle toxicity of paclitaxel did not adversely influence QOL. QOL data can contribute useful information on the experience of symptoms and their time course, which may assist patients and physicians in their discussion about the anticipated effects of therapy.

Abdominal Pain↗

PubMed2004

Prospective validation of serum CYFRA 21-1, beta-2-microglobulin, and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy.

BACKGROUND: Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21-1 (CYFRA), ferritin, and beta-2-microglobulin (beta2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively. METHODS: Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4-6 weeks after the completion of RT. Pre-RT and post-RT levels of serum CYFRA, ferritin, and beta2M were analyzed and correlated with overall survival (OS), progression-free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre-RT and post-RT plasma Epstein-Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification. RESULTS: Sixty percent of patients had International Union Against Cancer Stage III-IV disease. At a median follow-up of 116 weeks (range, 37-239 weeks), 38 patients had disease progression. On multivariate analysis, pre-RT CYFRA and post-RT EBV DNA levels were independent predictors of poor OS, post-RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre-RT CYFRA levels > or = 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10-1.26) compared with patients who had pre-RT CYFRA levels < 1.5 U/mL. There were no associations between age, post-RT CYFRA levels and pre-RT or post-RT serum ferritin and beta2M levels, and the survival and recurrence rates on multivariate analysis. CONCLUSIONS: Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT.

Adolescent↗

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

Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group.

BACKGROUND: The current study was conducted to examine the pattern and the predictive factors of distant metastases (DM) in patients with nasopharyngeal carcinoma (NPC) after primary radiotherapy treatment. METHODS: Data from all five regional cancer centers in Hong Kong were collected retrospectively and pooled for the current study, which was coordinated by the Hong Kong Nasopharyngeal Carcinoma Study Group. The sample was comprised of all 2915 patients with NPC without DM at the time of presentation who were treated with radiotherapy in 1 of the 5 cancer centers during the period between January 1996 and December 2000. RESULTS: DM was found to be the leading cause of NPC failure, with a 5-year actuarial rate of 14.9% in this patient cohort. Despite the poor overall survival (OS) of these patients, those with lung metastasis alone represented a distinctive group associated with a significantly better OS. International Union Against Cancer (UICC) N classification, UICC T classification, advanced age, and male gender were found to be significant and independent determinants for DM. CONCLUSIONS: Long-term survival is possible in patients with distant metastatic NPC confined to the lung. An aggressive approach to treatment for this group of patients should be considered.

Adult↗

PubMed2004

Association of human-leukocyte-antigen class I (B0703) and class II (DRB10301) genotypes with susceptibility and resistance to the development of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a public health concern worldwide. By studying the human leukocyte antigen (HLA) types A, B, DR, and DQ alleles in 90 Chinese patients with serologically confirmed SARS infections, we identified a strong association between HLA-B*0703 (OR, 4.08; 95% CI, 2.03-8.18; P=.00072 [Bonferroni-corrected P value, P(c) <.0022]) and -DRB1*0301 (OR, 0.06; 95%, 0.01-0.47; P=.00008 [after Bonferroni correction, P<.0042]) and the development of SARS. Moreover, the frequency of B*0703 and B60 coinheritance (9.6%; 95% CI, 4.6%-19.0%) in our SARS group was significantly higher (P=3x10(-9)) than that expected in the general population (0.4%). These genetic data will critically affect both the study of the pathogenesis of SARS and the design of vaccination programs.

Adult↗