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Biomedical subjects

J F Tierney

Publications and source records attributed to J F Tierney.

14 recordsLinked to original sources
PubMed2006

Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration.

BACKGROUND: Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women. PATIENTS AND METHODS: We carried out systematic searches for randomised controlled trials (RCTs) comparing chemotherapy with another intervention. Data were extracted from trial reports or supplied by investigators. Where possible, hazard ratios (HRs) were calculated for OS and PFS and odds ratios (ORs) were calculated for acute toxicity. The impact of more versus less intensive chemotherapy on OS, PFS and acute toxicity was assessed in a meta-analysis. RESULTS: Eleven eligible RCTs were identified that recruited 2288 patients. A meta-analysis of six of these trials found that PFS [HR = 0.80, 95% confidence interval (CI) 0.71-0.90; P = 0.004], but not OS (HR = 0.90, 95% CI 0.80-1.03; P = 0.12), was significantly improved when more intensive chemotherapy was compared with less intensive chemotherapy. OS was improved when doxorubicin, cisplatin and other drugs were compared with doxorubicin and cisplatin. Toxicity was generally higher with more chemotherapy. There was insufficient evidence to assess the effect of chemotherapy on symptom control or quality of life (QoL). Platinums, anthracyclines and taxanes were the most studied in phase II trials and combinations gave the best responses, but patient selection and pre-treatment was very variable. CONCLUSIONS: More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.

Antineoplastic Agents↗
PubMed2005

Preoperative radiotherapy for esophageal carcinoma.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. AUTHORS' CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed2004

Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix: a systematic review.

We identified eight randomised control trials of hydroxyurea and radiation versus radiotherapy alone (six published in full and two abstracts). Most concluded that outcomes were improved by use of hydroxyurea. However, methodological problems associated with these trials included small sample size, a large number of patient exclusions post randomisation, differing outcome definitions, subgroup analyses of already small numbers of patients and questionable rules for censoring, particularly a failure to include treatment related deaths in the survival analysis. All but two studies were of less than 50 patients. Patients were excluded from some analyses for treatment related reasons. The exclusion of such patients undoubtedly altered the conclusions of the studies. Even if there was a survival advantage attributed to hydroxyurea, overall survival was somewhat poor. We found the evidence regarding the use of hydroxyurea and radiotherapy to be inadequate for assessing its role in the treatment of cervical cancer.

Antineoplastic Agents↗
PubMed2001

Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis.

BACKGROUND: The US National Cancer Institute alert in February, 1999, stated that concomitant chemotherapy and radiotherapy should be considered for all patients with cervical cancer. Our aim was to review the effects of chemoradiotherapy on overall and progression-free survival, local and distant control, and acute and late toxicity in patients with cervical cancer. METHODS: With the methodology of the Cochrane Collaboration, we did a systematic review of all known randomised controlled trials done between 1981 and 2000 (17 published, two unpublished) of chemoradiation for cervical cancer. FINDINGS: The trials included 4580 randomised patients, and 2865-3611 patients (62-78%) were available for analysis. Cisplatin was the most common agent used. The findings suggest that chemoradiation improves overall survival (hazard ratio 0.71, p<0.0001), whether platinum was used (0.70, p<0.0001) or not (0.81, p=0.20). A greater beneficial effect was seen in trials that included a high proportion of stage I and II patients (p=0.009). An improvement in progression-free survival was also seen with chemoradiation (0.61, p<0.0001). Thus, the absolute benefit in progression-free and overall survival was 16% (95% CI 13-19) and 12% (8-16), respectively. A significant benefit of chemoradiation on both local (odds ratio 0.61, p<0.0001) and distant recurrence (0.57, p<0.0001) was also recorded. Grade 3 or 4 haematological (odds ratio 1.49-8.60) and gastrointestinal (2.22) toxicities were significantly greater in the concomitant chemoradiation group than the control group. There was insufficient data to establish whether late toxicity was increased in the concomitant chemoradiation group. INTERPRETATION: Concomitant chemotherapy and radiotherapy improves overall and progression-free survival and reduces local and distant recurrence in selected patients with cervical cancer, which may give a cytotoxic and sensitisation effect.

Antineoplastic Agents↗
PubMed2000

Preoperative radiotherapy for esophageal carcinoma. Oeosphageal Cancer Collaborative Group.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: Medline and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. REVIEWER'S CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed2000

Is there bias in the publication of individual patient data meta-analyses?

OBJECTIVE: There is increasing empirical evidence for the existence of bias in the publication of primary clinical research, with statistically significant results being published more readily, more quickly, and in higher impact journals. Meta-analysis of individual patient data (IPD) may represent a gold standard of "secondary" clinical research, giving the best possible summary of current evidence for a particular question, but publication of these may also be subject to bias. This study aimed to explore which factors might be associated with publication of IPD meta-analyses and to identify potential sources of bias. METHODS: For all known IPD meta-analysis projects in cancer, the responsible investigator was surveyed by means of a questionnaire to determine descriptive characteristics of the meta-analysis, the nature of the results, and details of the publication history. RESULTS: There is no good evidence that overall publication status of meta-analyses in cancer is dependent on the statistical or clinical significance of the results. However, those meta-analyses with nonsignificant results did seem to take longer to publish and were published in lower impact journals compared with those with more striking results. CONCLUSIONS: Based on the current data, there seems to be no strong association between the results of IPD meta-analyses in cancer and publication.

Humans↗
PubMed1999

Can the published data tell us about the effectiveness of neoadjuvant chemotherapy for locally advanced cancer of the uterine cervix?

The effect of neoadjuvant chemotherapy on survival of patients with locally advanced cervical cancer was investigated by conducting a systematic review and meta-analysis of the published data. Of the 21 randomised trials that we identified, only 15 were published. Furthermore, 2-year survival data could be extracted from only seven trial reports and 3-year survival from only nine trial reports. Meta-analyses of the published data at 2 and 3 years are neither clearly in favour of neoadjuvant chemotherapy nor control (2 years: odds ratio (OR) = 1.09, 95% confidence interval (CI) = 0.83-1.45, P = 0.37; 3 years: OR = 0.96, 95% confidence interval (CI) = 0.73-1.25, P = 0.45). Being restricted to only some of the data from a relatively small fraction of the randomised trials, these analyses potentially suffer from a number of biases and are therefore inconclusive. The only reliable way to judge the value of neoadjuvant chemotherapy in this disease is to perform a meta-analysis of centrally collected, updated, individual data on all patients from all known randomised trials. Such an analysis is currently being carried out by an international collaborative group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group).

PURPOSE: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Carcinoma↗
PubMed1995

Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials.

Fifteen published randomised trials comparing adjuvant chemotherapy with no chemotherapy in soft-tissue sarcoma (STS) were identified (1546 patients). A qualitative review and a meta-analysis of this published literature were performed. With the qualitative review it was not possible to synthesise the apparently conflicting results of individual trials. The meta-analysis of the published data suggests an improvement in survival at 2 years (OR = 0.73, 95% CI = 0.53-0.99, P = 0.044) and at 5 years (OR = 0.59, 95% CI = 0.45-0.78, P = 0.0002) in favour of chemotherapy. However, the assumptions and approximations required to conduct this quantitative summary demand that the results are interpreted with caution. The only reliable means of assessing the current evidence on whether adjuvant chemotherapy has a role in the treatment of patients with STS, is to collect, check and reanalyse individual patients data (IPD) from each trial centrally, and formally combine the results in a stratified time-to-event analysis. Such an IPD analysis is currently being undertaken by an international collaborative group.

Adult↗
PubMed1995

The tapeworm Schistocephalus solidus alters the activity and response, but not the predation susceptibility of infected copepods.

Cyclops abyssorum and Cyclops scutifer were experimentally infected with procercoids of the cestode Schistocephalus solidus, then examined for altered behavior and susceptibility to predation, respectively. Infected C. abyssorum differed from uninfected controls in their initial response to disturbance and their degree of activity but only when they harbored procercoids that were potentially infective to the next host. To examine the possible consequence of the altered behavior for susceptibility to predation, three-spined sticklebacks (Gasterosteus aculeatus) were offered equal numbers of infected and uninfected C. scutifer. Infected copepods were not preyed upon significantly more than controls.

Analysis of Variance↗
PubMed1992

Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis.

CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5-6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS damage associated with sub-curative chemotherapy.

Animals↗
PubMed1992

Infectivity of plerocercoids of Schistocephalus solidus (Cestoda: Ligulidae) and fecundity of the adults in an experimental definitive host, Gallus gallus.

Aspects of the infectivity of the plerocercoid stage and the fecundity of the adult stage of Schistocephalus solidus were examined using the chicken, Gallus gallus, as an experimental host. To investigate size-related infectivity of the plerocercoid stage to a definitive host, a range of plerocercoids (166) were weighed, and each was fed to an individual male chicken. Only a very small percentage of plerocercoids weighing less than 50 mg established compared with in excess of 50% in all other weight classes. To examine the factors affecting the quantity of eggs produced by the adult stage, 15 similar-sized plerocercoids (160-218 mg) were fed to chickens. The majority of plerocercoids administered established as adults and survived until the experiment was terminated on day 7 postinfection (PI). Fecal egg counts indicated that all established worms commenced egg production on day 2 PI with peak output on day 2 or 3 PI. By day 7 PI, egg production in the surviving worms had declined, but it was still evident. The final weight of the adult and the average egg output per worm were unrelated to the initial weight of the infecting plerocercoid. However, the average egg output was predicted by the final adult dry weight and to a lesser extent by the proportion of weight lost in the transition from plerocercoid to adult, but not by the absolute weight loss.

Analysis of Variance↗
PubMed1983

Zymosan activation of plasma reduces hypoxic pulmonary vasoconstriction.

Small doses of endotoxin (15 micrograms/kg IV) inhibit the pulmonary vascular pressor response to alveolar hypoxia in the anesthetized dog. One of the actions of endotoxin is to initiate the alternate pathway of complement activation. Incubation of human plasma with zymosan (ZAP) will activate this pathway. We wished to see if ZAP would mimic the effect of endotoxin. Prior to ZAP, hypoxia (F1O2 12%) in 5 anesthetized dogs increased pulmonary vascular resistance (PVR: mm Hg/L/min) from 3.7 +/- 0.8 to 7.1 +/- 1.5. After 50 ml ZAP IV the PVR change with hypoxia was only from 3.6 +/- 0.6 to 3.9 +/- 0.8. Plasma heated to destroy complement prior to ZAP incubation in one experiment did not reduce the pressor response. In a further 5 dogs pretreated with meclofenamate (2 mg/kg IV) the PVR increased from 3.7 +/- 0.4 to 7.5 +/- 0.4 with hypoxia prior to IV ZAP and from 4.4 +/- 0.5 to 6.5 +/- 0.6 after ZAP. The effect of ZAP indicates that endotoxin may work through the activation of complement. The protection of the hypoxic pressor response by meclofenamate suggests that the ZAP inhibition (like endotoxin inhibition) may involve dilator prostaglandin-like substances.

Animals↗