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Benny Zee

Publications and source records attributed to Benny Zee.

At least 37 records · Page 2Linked to original sources
PubMed2004

Determining the relationship between toxicity and quality of life in an ovarian cancer chemotherapy clinical trial.

PURPOSE: This analysis of data from a randomized trial of chemotherapy in epithelial ovarian cancer sought to determine whether a relationship exists between the presence and severity of the most commonly observed toxic effects and the corresponding quality of life (QOL) items. PATIENTS AND METHODS: One hundred fifty-two eligible patients accrued from Canada by the National Cancer Institute of Canada Clinical Trials Group on a randomized trial of paclitaxel and cisplatin versus cyclophosphamide/cisplatin were included in the analysis. Toxicity to the chemotherapeutic treatments was subjectively evaluated using a trial-specific checklist for ovarian cancer and the European Organization for Research and Treatment of Cancer QLQ C30+3 questionnaire. Assessments were conducted at baseline, before each cycle of treatment (3 weeks), and at each 3-month follow-up during the next 2 years (or until progression). RESULTS: The most frequently observed symptoms experienced during or shortly following chemotherapy were neurosensory loss, lethargy, nausea, vomiting, and alopecia. Regression analyses revealed that change scores of QOL items related to motor weakness and gastrointestinal pain were common predictors for the change global QOL score during protocol treatment; and change scores of QOL items related to lethargy or fatigue and change toxicity grade of mood predicted the change global QOL score after patients were off treatment. CONCLUSION: The use of the European Organization for Research and Treatment of Cancer QLQ C30+3 and trial-specific checklist was able to assess the effect of expected toxicities on patient' s QOL during and following treatment, and so may be useful in addressing the concerns regarding methodological issues that have limited the acquisition of prospective, longitudinal treatment-related toxicity data.

Antineoplastic Combined Chemotherapy Protocols↗
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

Comparison of CT and MR imaging for the detection of extranodal neoplastic spread in metastatic neck nodes.

PURPOSE: To compare computed tomography (CT) and magnetic resonance (MR) imaging for the detection of extranodal neoplastic spread (ENS) in metastatic cervical nodes from head and neck squamous cell carcinoma. MATERIALS AND METHODS: 17 patients with a squamous cell carcinoma of the head and neck underwent CT and MR imaging. The neck nodes were assessed for ENS and the results compared using pathology from the surgical resection. RESULTS: Radiologic-pathologic correlation was performed in 51 malignant nodes. The accuracy, sensitivity and specificity were respectively 73, 65, 93% for CT, and 80, 78, 86% for MR imaging. Comparison of CT and MR imaging showed that there was no significant difference between the two modalities for either sensitivity (P = 0.1317) or specificity (P = 0.3173). CONCLUSION: CT and MR imaging are comparable for the detection of ENS.

Aged↗
PubMed2003

Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein-Barr virus DNA and anti-Epstein-Barr viral capsid antigen IgA antibody.

BACKGROUND: Circulating Epstein-Barr viral (EBV) DNA and anti-EBV capsid antigen IgA (IgA VCA) represent two of the most sensitive peripheral blood markers of nasopharyngeal carcinoma (NPC), but direct comparative studies of these two markers are lacking. METHODS: The sensitivities and specificities of IgA-VCA and EBV DNA for diagnosis of NPC were determined in 139 new cases of NPC and 178 healthy individuals, respectively. EBV DNA was also assessed in 36 healthy family members identified as having false-positive IgA-VCA results at a screening clinic. EBV DNA was measured by a real-time quantitative PCR assay with a detection limit of 60 copies/mL. IgA-VCA was measured by semiquantitative indirect immunofluorescent method; a titer > or =1/10 was taken as positive. RESULTS: The sensitivities of EBV DNA and IgA-VCA for diagnosis of NPC were 95% (95% confidence interval, 91-98%) and 81% (73-87%), respectively. The combined marker panel had an overall sensitivity (positive result by either marker) of 99%. The concentrations of both markers showed dependence on cancer stage. The specificities of EBV DNA and IgA-VCA were 98% (96-99%) and 96% (91-98%), respectively. Among 36 healthy family members with false-positive IgA-VCA results, three-fourths had undetectable EBV DNA, whereas the others had increased EBV DNA concentrations that were significantly lower than in NPC patients. CONCLUSIONS: For diagnosis of NPC, EBV DNA identifies almost all false-negative IgA-VCA cases and gives a 99% diagnostic sensitivity when combined with IgA-VCA. In the screening setting, EBV DNA identifies three-fourths of false-positive IgA-VCA cases. The selective application of EBV DNA in an IgA-VCA-based screening protocol could improve screening accuracy with only moderate increases in cost.

Adult↗
PubMed2003

Disparity of sensitivities in detection of radiation-naïve and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein-Barr virus DNA1,2.

PURPOSE: The purpose of this research was to compare the sensitivities of plasma EBV DNA in detection of postirradiation locally recurrent nasopharyngeal carcinoma (NPC), postirradiation distant metastatic NPC, and radiation-naïve NPC. EXPERIMENTAL DESIGN: Twenty-four patients with postirradiation local recurrence of NPC were assessed for plasma EBV DNA levels by a real-time quantitative PCR system. The results were compared with those of a cohort of 140 patients with newly diagnosed NPC and with those of 25 patients with distant metastatic relapse. EBV-encoded RNA positivity was also assessed in locally recurrent tumors and newly diagnosed tumors with undetectable plasma EBV DNA levels. RESULTS: Postirradiation locally recurrent tumors were associated with a significantly lower rate of detectable plasma EBV DNA compared with radiation-naïve tumors of comparable stage [stage I-II tumors: 5 of 12 (42%) versus 47 of 51 (92%), P = 0.0002; stage III-IV tumors: 10 of 12 (83%) versus 88 of 89 (99%), P = 0.01; Fisher's exact test], and compared with distant metastatic recurrences [15 of 24 (63%) versus 24 of 25 (96%), P < 0.02; Fisher's exact test]. The median EBV DNA level in patients with detectable EBV DNA was also significantly lower in locally recurrent tumors than in radiation-naïve tumors. All of the tissue samples of tumors associated with undetectable EBV DNA levels, where available, were EBV-encoded RNA positive. CONCLUSIONS: The sensitivity of EBV DNA in the detection of tumors regrowing from an irradiated site is much lower than that from a radiation-naïve site. Although plasma EBV DNA is very effective in detecting distant metastatic relapse of NPC, it cannot be relied on as the sole surveillance tool for detection of local relapse.

Antigens, Viral↗
PubMed2003

Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type.

BACKGROUND: Patients with International Union Against Cancer (UICC) Stage I-II nasopharyngeal carcinoma (NPC) appear to have a relatively favorable prognosis and generally are excluded from trials of combined modality treatment. More recently, plasma/serum cell-free Epstein-Barr virus (EBV) DNA has been shown to be measurable in the majority of NPC patients at the time of diagnosis, and appears to have prognostic significance. However, within Stage I-II disease, in which failure events are infrequent, the prognostic impact of the pretreatment EBV DNA level has not been addressed to our knowledge. This issue has management implications because different therapeutic strategies currently are employed for patients with good-risk and those with poor-risk NPC. METHODS: A cohort of 90 patients with UICC Stage I-II NPC (World Health Organization Grade 2/3 histology) had their pretherapy plasma/serum EBV DNA levels determined by a quantitative polymerase chain reaction assay and correlated with the probability of posttherapy failure. All patients received radiation therapy only, except for three patients who also received concurrent chemotherapy. Kaplan-Meier plots of the probability of locoregional failure, distant failure, and cancer-specific survival were compared with reference to clinical stage and EBV DNA levels. RESULTS: With a median follow-up time of 45 months, 12 patients and 7 patients, respectively, had developed locoregional and distant failures, including 2 patients with both local and distant failures. Patients with distant failure had significantly higher pretherapy EBV DNA levels than those without failure (a median of 13,219 copies/mL [interquatile-range, 274,635 copies/mL] vs. a median of 423 copies/mL [interquatile-range, 2753 copies/mL]). The probability of distant failure was significantly higher in patients with high (>4000 copies/mL plasma) compared with low EBV DNA levels (P=0.0001, log-rank test) and for Stage IIB disease compared with Stage I and Stage IIA disease combined (P=0.0149, log-rank test), but was not significantly different between patients with Stage II and those with Stage I disease. The risks of locoregional failure were not significantly different between patients with high and those with low EBV DNA levels, and also was not significantly different between clinical substages. Approximately 35% of patients with Stage IIB disease were in the at-risk group for distant failure, as identified by high EBV DNA levels. CONCLUSIONS: Within a group of patients with UICC Stage I-II NPC, the pretherapy plasma EBV DNA level was found to identify a poor-risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may warrant management considerations currently applicable only to cases of Stage III-IV disease. The prognostic significance of designating Stage IIB disease as per the 1997 UICC staging was confirmed, although the pretherapy EBV DNA level appears to be a more powerful prognostic discriminator in patients with early-stage NPC.

DNA, Viral↗
PubMed2003

Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier?

PURPOSE: To evaluate the enrollment of older patients (>/= 65 years) in Canadian cancer treatment trials and compare accrual of older patients in Canada and the United States. PATIENTS AND METHODS: A retrospective analysis of the number of older patients enrolled in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) treatment trials between 1993 and 1996 was performed. These rates were compared with the corresponding rates in the general population of patients who were >/= 65 years old and had cancer, obtained from Statistics Canada, and those published by the Southwest Oncology Group (SWOG) in the United States. RESULTS: Between 1993 and 1996, 4,174 patients were enrolled onto 69 NCIC CTG trials of 16 tumor types. Older patients accounted for 22% of trial enrollees, compared with 58% of the Canadian population with cancer. This discrepancy existed in all cancer types except for multiple myeloma. The percentages of older patients enrolled were also analyzed by study type: 15% in adjuvant trials, 25% in metastatic trials, 29% in investigational new drug trials, 24% in phase I trials, and 21% in supportive care trials. The overall proportion of older patients enrolled onto Canadian trials (22%) was slightly lower than that in SWOG trials (25%). CONCLUSION: Age remains a barrier for accrual onto cancer treatment trials, even when reimbursement is not an issue. Strategies to overcome this barrier, including the implementation of trials specifically tailored to patients aged >/= 65 years, are prudent in light of our aging population.

Age Factors↗
PubMed2003

Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma--a prospective study.

BACKGROUND: This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC). METHODS: Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage. RESULTS: On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP. CONCLUSIONS: EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease.

Adult↗
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↗
PubMed2002

Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer.

PURPOSE: Increased expression of metalloproteinases is associated with poor prognosis in small-cell lung cancer (SCLC). This trial was undertaken to determine whether adjuvant treatment with the metalloproteinase inhibitor marimastat could prolong survival in responding patients with SCLC after chemotherapy. PATIENTS AND METHODS: SCLC patients in complete or partial remission were eligible. They were stratified by radiotherapy (early, late, or none), stage (extensive or limited), response (complete or partial), and cooperative group (National Cancer Institute of Canada-Clinical Trials Group or European Organization for Research and Treatment of Cancer). They were randomized to receive marimastat 10 mg or placebo orally bid for up to 2 years. RESULTS: There were 532 eligible patients (266 marimastat and 266 placebo). Stage was limited for 279 patients (52%) and extensive for 253 (48%). Best response to induction therapy was complete remission for 176 patients (33%), partial remission for 341 (64%), and 15 patients (3%) had undergone surgical resection. The median time to progression for marimastat patients was 4.3 months compared with 4.4 months for placebo patients (P =.81). Median survivals for marimastat and placebo patients were 9.3 months and 9.7 months, respectively (P =.90) Toxicity was generally limited to musculoskeletal symptoms (18% grade 3/4 for marimastat). Dose modifications for musculoskeletal toxicity were required in 90 patients (33%) on the marimastat arm, and 87 (32%) permanently stopped marimastat because of toxicity. Patients on marimastat had significantly poorer quality of life at 3 and 6 months. CONCLUSION: Treatment with marimastat after induction therapy for SCLC did not result in improved survival and had a negative impact on quality of life.

Adult↗
PubMed2002

Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma.

BACKGROUND: Epstein-Barr virus (EBV) DNA can be detected and quantified in the plasma of patients with EBV-related tumors, such as nasopharyngeal carcinoma (NPC). Although NPC at early stages can be cured by radical radiotherapy, there is a high recurrence rate in patients with advanced NPC. The pretreatment level of circulating EBV DNA is a prognostic factor for NPC, but the prognostic value of post-treatment EBV DNA has not been studied. We designed a prospective study in Hong Kong, China, to investigate the value of plasma EBV DNA as a prognostic factor for NPC. METHODS: One hundred seventy NPC patients, without metastatic disease at presentation, were treated with a uniform radiotherapy protocol. Circulating EBV DNA was measured by real-time quantitative polymerase chain reaction before treatment and 6-8 weeks after radiotherapy was completed. Risk ratios (RRs) were determined with a Cox regression model, and associations of various factors with progression-free and overall survival and recurrence rates were determined with a stepwise Cox proportional hazards model. All statistical tests were two-sided. RESULTS: Ninety-nine percent of patients achieved complete clinical remission. Levels of post-treatment EBV DNA dominated the effect of levels of pretreatment EBV DNA for progression-free survival. The RR for NPC recurrence was 11.9 (95% confidence interval [CI] = 5.53 to 25.43) for patients with higher post-treatment EBV DNA and 2.5 (95% CI = 1.14 to 5.70) for patients with higher pretreatment EBV DNA. Higher levels of post-treatment EBV DNA were statistically significantly associated with overall survival (P<.001; RR for NPC recurrence = 8.6, 95% CI = 3.69 to 19.97). The positive and negative predictive values for NPC recurrence for a higher level of post-treatment EBV DNA were 87% (95% CI = 58% to 98%) and 83% (95% CI = 76% to 89%), respectively. CONCLUSION: Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load.

Adult↗
PubMed2002

A Phase I-II study of sequential administration of topotecan and oral etoposide (toposiomerase I and II inhibitors) in the treatment of patients with small cell lung carcinoma.

BACKGROUND: Topotecan (9-dimethylaminomethyl-10-hydroxycampthothecin) is a new topoisomerase I inhibitor with promising efficacy in the treatment of patients with small cell lung carcinoma (SCLC). Combination with a topoisomerase II inhibitor may potentate the therapeutic effect of topotecan, although there has been conflicting preclinical information on the combination. The objectives of this study were to establish the maximum tolerated dose and to determine the efficacy of the sequential combination of intravenous topotecan and oral etoposide in the treatment of patients with SCLC. METHODS: Patients with histologically confirmed, limited or extensive stage SCLC were eligible. The dose escalation scheme of three cohorts (six patients per cohort) started at intravenous topotecan 0.5 mg/m(2) per day for 5 days and oral etoposide 50 mg twice daily for 7 days (21-day cycles). Subsequent dose levels involved escalation of topotecan to 0.75 mg/m(2) per day and 1.0 mg/m(2) per day for 5 days. A Phase II study was conducted at one dose level below the maximum tolerated dose. The authors alternated the drug sequence with each consecutive cycle and compared the hematologic toxicity between the two sequences. RESULTS: Thirty-six patients (21 patients with limited disease and 15 patients with extensive disease) received a total of 173 courses of sequential combination chemotherapy (topotecan --> etoposide, 88 courses; etoposide --> topotecan, 85 courses). The authors identified dose levels for the Phase II study as follows: topotecan, 0.75 mg/m(2) per day for 5 days; and etoposide, 50 mg twice daily for 7 days. The dose-limiting toxicity was neutropenia. At this dose level, the incidence of Grade 3-4 neutropenia and the incidence of Grade 3-4 thrombocytopenia were 25% and 10.9%, respectively. Two patients died from neutropenic sepsis. There was no significant difference in hematologic toxicities between the two sequences. Complete and partial response rates were 5.6% and 55.6%, respectively (limited disease, 9.5% and 66.75%; extensive disease, 0% and 40%, respectively). The median progression free survival was 31.9 weeks (limited disease, 36.1 weeks; extensive disease, 28.9 weeks; 95% confidence interval, 25.6-36.0 weeks), and the median overall survival was 52.4 weeks (limited disease, 54.9 weeks; extensive disease, 30.1 weeks; 95% confidence interval, 39.6-57.7 weeks). CONCLUSIONS: Combination therapy with topoisomerase I and II inhibitors is a safe and effective regimen for patients with SCLC. Future research on this combination should focus on an oral regimen for patients with extensive disease and poor tolerance to cisplatin. The authors recommend an oral dosage of topotecan at 1.2 mg/m(2) per day (equivalent to intravenous topotecan at 0.75 mg/m(2) per day) for 5 days followed by etoposide 50 mg twice daily for 7 days.

Administration, Oral↗
PubMed2002

Quantitative measurement of post-irradiation neck fibrosis based on the young modulus: description of a new method and clinical results.

BACKGROUND: Postirradiation fibrosis is one of the most common late effects of radiation therapy for patients with head and neck carcinoma. An objective and quantitative method for its measurement is much desired, but the criteria currently used to score fibrosis are mostly semiquantitative and partially subjective. METHODS: The Young Modulus (YM) is a physical parameter that characterizes the deformability of material to stress. The authors measured the YM in soft tissues of the neck, at defined reference points, using an ultrasound probe and computer algorithm that quantified the indentation (deformation) on tissue due to a measured, applied force. One hundred five patients who had received previous radiation therapy to the entire neck were assessed, and the results were compared with the hand palpation scores and with a functional parameter represented by the range of neck rotation, and all results were correlated with symptoms. RESULTS: The YM was obtained successfully in all patients examined. It had a significant positive correlation with the palpation score and a significant negative correlation with the range of neck rotation. The YM was significantly higher on the side of the neck that received a boost dose of radiation, although the corresponding palpation scores were similar. The results of all three measurement methods were correlated with symptoms. CONCLUSIONS: Postirradiation neck fibrosis can be measured in absolute units based on the YM. The results showed a significant correlation with hand palpation scores, with restriction of neck rotation, and with symptoms. Compared with the palpation method, the YM is more quantitative, objective, focused on small subregions, and better discriminates regions subject to differential radiation dose levels. Its inclusion in the Analytic category of the Late Effects of Normal Tissues-SOMA system should be considered to facilitate comparative studies.

Dose-Response Relationship, Radiation↗
PubMed2002

Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.

BACKGROUND: External-beam radiotherapy (delivered either preoperatively or postoperatively) is frequently used in local management of sarcomas in the soft tissue of limbs, but the two approaches differ substantially in their potential toxic effects. We aimed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults. METHODS: After stratification by tumour size (< or = 10 cm or >10 cm), we randomly allocated 94 patients to preoperative radiotherapy (50 Gy in 25 fractions) and 96 to postoperative radiotherapy (66 Gy in 33 fractions). The primary endpoint was rate of wound complications within 120 days of surgery. Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes. FINDINGS: Median follow-up was 3.3 years (range 0.27-5.6). Four patients, all in the preoperative group, did not undergo protocol surgery and were not evaluable for the primary outcome. Of those patients who were eligible and evaluable, wound complications were recorded in 31 (35%) of 88 in the preoperative group and 16 (17%) of 94 in the postoperative group (difference 18% [95% CI 5-30], p=0.01). Tumour size and anatomical site were also significant risk factors in multivariate analysis. Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment (p=0.0481). INTERPRETATION: Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy, the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy, and the size and anatomical site of the tumour.

Aged↗
PubMed2002

Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients.

BACKGROUND: The current TNM staging system for patients with hepatocellular carcinoma (HCC) does not include liver function parameters and does not provide a precise prognosis for patients in different risk groups. The objectives of this study were to construct a new prognostic index for patients with hepatocellular carcinoma, the Chinese University Prognostic Index (CUPI), and to compare it with existing staging systems in terms of their ability to classify patients into different risk group. METHODS: From 1996 to 1998, 926 ethnic Chinese patients who were diagnosed with HCC (mainly hepatitis B-associated) at a single institution were recruited prospectively into this study. A multivariate analysis on 19 patient characteristics was performed using a Cox regression model to identify independent prognostic factors. Weights were derived from the regression coefficients of various factors to construct the CUPI. Patients were classified according to different staging systems. Survival curves were plotted with the Kaplan-Meier method and were compared by using a log-rank test. RESULTS: Both the TNM staging system and the Okuda staging system had prognostic significance, but the significance was lower for the Cancer of the Liver Italian Program (CLIP) prognostic score among the patients in the study population. The CUPI was constructed by adding the following factors into the TNM staging system: total bilirubin, ascites, alkaline phosphatase, alpha fetoprotein, and asymptomatic disease on presentation. The new CUPI characterized three risk groups with highly significant differences in survival during the whole period of follow-up (P < 0.00001) and was more discriminant than the other systems. CONCLUSIONS: In the study population of patients with mainly hepatitis B-associated HCC, the CUPI was more discriminant than the TNM staging system, the Okuda staging systems, or the CLIP prognostic score in classifying patients into different risk groups and was better at predicting survival. The CUPI needs to be validated by different cohorts of patients before it can be recommended for general use.

Adult↗
PubMed2002

Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy.

BACKGROUND: The objective of the current study was to identify patient and disease related factors that influence response and survival for patients with unresectable hepatocellular carcinoma (HCC) who received a systemic combination chemotherapy consisting of cisplatin, alpha-interferon, doxorubicin, and 5-fluorouracil (PIAF). METHODS: From July 1996 to February 1999, 149 patients with unresectable HCC were treated with PIAF: cisplatin (20mg/m2 intravenously, Days 1-4), doxorubicin (40mg/m2 intravenously, Day 1), 5-fluorouracil (400mg/m2 intravenously, Days 1-4), and alpha-interferon (5MU/m2 subcutaneously, Days 1-4), once every 3 weeks up to a maximum of six cycles. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting response and survival. RESULTS: The objective response rate according to conventional criteria was 16.8% (complete response in 3 out of 149 patients, or 2%, 95% confidence interval [CI] 0-4.3%; partial response in 22 out of 149 patients, or 14.8%, 95% CI 9-20%). The median survival time was 30.9 weeks (95% CI 22.1 to 40). Significant independent predictors of an objective response were: absence of cirrhosis (P = 0.006), low bilirubin level (P = 0.006), and positive hepatitis C serology (P = 0.025). The following factors were related to a shorter survival time: high Okuda stage (P = 0.001), vascular involvement (P = 0.018), and cirrhosis (P = 0.008). Good risk patients (absence of cirrhosis and total bilirubin < or = 0.6mg/dL) had an objective response rate of 50%. CONCLUSIONS. Patients with unresectable HCC who also have normal total bilirubin and non-cirrhotic livers have a better chance of response and prolonged survival after treatment with systemic PIAF.

Adolescent↗
PubMed2002

Factors affecting workload of cancer clinical trials: results of a multicenter study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials' task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow-up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use.

Cancer Care Facilities↗