Risk factors for local recurrence in Wilms tumour and the potential influence of biopsy - the United Kingdom experience.

RATIONALE: The UKW3 trial compared biopsy/pre-operative chemotherapy versus immediate nephrectomy and afforded the opportunity to examine the influence of percutaneous retroperitoneal biopsy and other factors on local and distant relapse of Wilms tumour (WT). METHODS: Patients with unilateral WT (stages I-IV) excluding metachronous relapse or early progressive disease were eligible. Metastatic and 'inoperable' tumours were biopsied electively. 'Local' was defined as relapse within the abdomen, except for liver metastases considered as 'distant' relapse, together with other haematogenous routes. Uni- and multivariable analyses estimated the risk factors for relapse. RESULTS: Overall, 285/635 (44.9%) patients had a biopsy. With a median follow-up of 10.1 years, 35 (5.5%) patients experienced a 'local', 15 a combined (2.4%) and 60 (9.4%) a 'distant' relapse. On univariate analysis, biopsy, anaplasia and tumour size were associated with an increased risk of local relapse. On multivariable analysis, anaplasia and tumour size remained significant for local relapse whereas the elevated risk of biopsy (hazards ratio (HR) = 1.80: 95% confidence interval (CI) 0.97-3.32, p = 0.060) was marginal. Age, anaplasia, tumour size, lymph nodes metastases and stage, but not biopsy, were individually associated with increased risk of distant relapse but only age and anaplasia remained significant following multivariable analysis. CONCLUSIONS: The UKW3 trial provides some reassurance that biopsy should not automatically lead to 'upstaging' of WT. Further assessment of this controversial area is required. Comparison of local relapse rates in a multinational trial in which the United Kingdom (UK) continued the practice of routinely biopsying all patients in contrast to the standard European approach will afford this opportunity and is planned.

The role of post-operative radiographs in predicting risk of flexor pollicis longus tendon rupture after volar plate fixation of distal radius fractures - a case control study.

BACKGROUND AND AIM: Volar plating of distal radius fractures is one of the common procedures performed in trauma surgery. Flexor pollicis longus (FPL) rupture has been described as complication following volar plating of distal radius fractures. The aim of our study was to investigate the possible relation between parameters measured on post-operative radiographs and the occurrence of FPL ruptures. MATERIALS AND METHODS: This was a case control study. The post-operative radiographs of 11 FPL rupture, and 22 non-FPL rupture patients were reviewed with respect to fracture reduction and plate position and the various parameters were calculated by five independent people. Logistic regression was used to examine the importance of the variables. RESULTS: We identified two significant factors to predict FPL rupture after volar plating of distal radial fractures. These were radial tilt and plate distance from the joint line. The odds ratio of ruptures was 0.74 (95% CI 0.57-0.95) for every degree of radial tilt <25° and 0.50 (95% CI 0.28-0.88) for every millimetre that the distal end of the plate was away from the volar lip of the distal radius at the wrist joint. CONCLUSION: Post-operative radiographs could help us predict FPL rupture after distal radius volar plating. The findings also highlight the need for good fracture reduction and thoughtful placement of the volar plate intraoperatively to minimise the risk of FPL tendon rupture.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC. METHODS: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life. RESULTS: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting. CONCLUSION: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial.

BACKGROUND: Radiotherapy is an effective adjuvant treatment for brain tumours arising in very young children, but it has the potential to damage the child's developing nervous system at a crucial time - with a resultant reduction in IQ leading to cognitive impairment, associated endocrinopathy and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with malignant brain tumours other than ependymoma, the results of which have already been published. METHODS: Ninety-seven children were enrolled between March 1993 and July 2003 and, following diagnostic review, comprised: medulloblastoma (n=31), astrocytoma (26), choroid plexus carcinoma [CPC] (15), CNS PNET (11), atypical teratoid/rhabdoid tumours [AT/RT] (6) and ineligible (6). Following maximal surgical resection, chemotherapy was delivered every 14 d for 1 year or until disease progression. Radiotherapy was withheld in the absence of progression. FINDINGS: Over all diagnostic groups the cumulative progression rate was 80.9% at 5 years while the corresponding need-for-radiotherapy rate for progression was 54.6%, but both rates varied by tumour type. There was no clear relationship between chemotherapy dose intensity and outcome. Patients with medulloblastoma presented as a high-risk group, 83.9% having residual disease and/or metastases at diagnosis. For these patients, outcome was related to histology. The 5-year OS for desmoplastic/nodular medulloblastoma was 52.9% (95% confidence interval (CI): 27.6-73.0) and for classic medulloblastoma 33.3% (CI: 4.6-67.6); the 5-year EFS were 35.3% (CI: 14.5-57.0) and 33.3% (CI: 4.6-67.6), respectively. All children with large cell or anaplastic variants of medulloblastoma died within 2 years of diagnosis. The 5-year EFS for non-brainstem high-grade gliomas [HGGs] was 13.0% (CI: 2.2-33.4) and the OS was 30.9% (CI: 11.5-52.8). For CPC the 5-year OS was 26.67% (CI: 8.3-49.6) without RT. This treatment strategy was less effective for AT/RT with 3-year OS of 16.7% (CI: 0.8-51.7) and CNS PNET with 1-year OS of 9.1% (CI: 0.5-33.3). INTERPRETATION: The outcome for very young children with brain tumours is dictated by degree of surgical resection and histological tumour type and underlying biology as an indicator of treatment sensitivity. Overall, the median age at radiotherapy was 3 years and radiotherapy was avoided in 45% of patients. Desmoplastic/nodular sub-type of medulloblastoma has a better prognosis than classic histology, despite traditional adverse clinical features of metastatic disease and incomplete surgical resection. A subgroup with HGG and CPC are long-term survivors without RT. This study highlights the differing therapeutic challenges presented by the malignant brain tumours of early childhood, the importance of surgical approaches and the need to explore individualised brain sparing approaches to the range of malignant brain tumours that present in early childhood.

Flexor pollicis longus tendon ruptures after palmar plate fixation of fractures of the distal radius.

Palmar plate fixation of distal radial fractures is becoming a standard treatment for this common injury. Ruptures of the extensor pollicis longus tendon have been reported in 8.6% of cases after this procedure. Although palmar plate fixation has also been associated with flexor pollicis longus (FPL) tendon problems, the majority of reported cases pre-date the use of newer anatomically precontoured locking plates. In this paper seven cases of FPL rupture are presented. This complication does not appear to be unique to one type of implant. The possible aetiologies for FPL ruptures are discussed and ways to reduce the incidence of this complication are suggested.

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Uruguay: development of tissues quality control and quality management system in the National Multi-Tissue Bank of Uruguay.

BNOT was created and regulated in 1977 and started its operation in 1978 according to the Decree No. 86/1977. By the Decree 248/005 is transformed in the National Institute of Donation and Transplantation of Cells, Tissues and Organs (Instituto Nacional de Donación y Trasplante de Células, Tejidos y Organos--INDT). The organisation has been operating within the State University Medical School and the Public Health Secretary and it is the governmental organisation responsible for the regulation, policy and management of donation and transplantation in Uruguay. By the Decree 160/2006 is responsible for human cells and tissues regulation too. The participation of the INDT in the IAEA program facilitated the introduction of the radiation sterilisation technique for the first time in the country. The radiation sterilisation of tissues processed by INDT (ex BNOT), was initially carried out in the 60 Cobalt Industrial Plant in the National Atomic Energy Commission of Argentina and now is carried out in INDT, using a Gamma Cell 220 Excel, which was provided by the IAEA through the national project URU/7/005. The results of the implementation of tissues, quality control and quality management system, are showed.

Concomitant (without adjuvant) temozolomide and radiation to treat glioblastoma: a retrospective study.

Between November 2004 and August 2006 we treated 35 patients with concomitant temozolomide (TMZ) and radiotherapy. Twelve patients had very large or multicentric glioblastoma multiforme with a poor performance status and received TMZ plus radiation doses of 45-50.4 Gy. The median survival of these patients was only 3.8 months. Twenty-three patients would have been eligible for randomisation in the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC) trial comparing combined and adjuvant TMZ plus radiation against radiotherapy alone. This group of patients received 60 Gy in 30 fractions plus concomitant TMZ (75 mg/m(2)) but no adjuvant chemotherapy. At a median follow-up of 26 months, five of 23 patients are alive. The median survival time was 17 months (1.43 years; 95% confidence interval 0.96-1.55). Eighteen per cent were alive at 2 years. Toxicity from TMZ was infrequent. This series adds to indirect evidence that the concomitant rather than the adjuvant is the more efficacious part of the EORTC/NCIC schedule for this type of patient. Further trials should include a concomitant chemoradiotherapy regimen as well as concomitant plus adjuvant chemotherapy.

Preliminary images from an adaptive imaging system.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.

Efficacy of carboplatin given in a phase II window study to children and adolescents with newly diagnosed metastatic soft tissue sarcoma.

AIM: The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. METHODS: Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. RESULTS: Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14-56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6-51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. CONCLUSION: Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma.

Response to N7 induction chemotherapy in children more than one year of age diagnosed with metastatic neuroblastoma treated in UKCCSG centers.

BACKGROUND: The highest reported metastatic response rate to induction chemotherapy in patients with neuroblastoma has been achieved by Kushner et al. [Kushner et al.: J Clin Oncol 12:2607-2613,1994; Cheung et al.: Med Pediatr Oncol 36: 227-230, 2001; Kushner et al.: J Clin Oncol 22:4888-4892, 2004] using their N6 and subsequently N7 protocols. This N7 induction was adopted by UKCCSG for new patients in 1999. METHODS: Forty-seven children with metastatic neuroblastoma were recruited between 1999 and 2002. They received the N7 intensive chemotherapy protocol, after full staging including evaluation by I123mIBG imaging where possible. RESULTS: Thirty patients with positive mIBG scans were evaluable for response, and complete resolution of metastatic disease was obtained in 16 (53.3%). Fourteen patients without positive mIBG scans were evaluated for response according to bone marrow and bone scan data and 11 (78.6%) cleared metastatic disease. The toxicity of this induction therapy was similar to that seen in previous UK protocols, although 14 patients had Brock grade 3 or 4 ototoxicity. Thirty-three patients proceeded to high-dose therapy with no unanticipated toxicities. For the whole group of 44 evaluable patients, the 3-year event-free survival (EFS) and overall survival (OS) were 38.3 and 46.7%, respectively. CONCLUSIONS: Although feasible in terms of delivery, when used in the UKCCSG centers, this protocol achieved a much lower response rate than in the previously published series in the US [Kushner et al.: J Clin Oncol 12:2607-2613,1994; Cheung et al.: Med Pediatr Oncol 36: 227-230, 2001; Kushner et al.: J Clin Oncol 22:4888-4892, 2004].

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison.

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.

Establishing long-term survival and cure in young patients with Ewing's sarcoma.

This paper investigates the potential for long-term survivorship for young patients diagnosed with Ewing's sarcoma. Data are examined from two successive UKCCSG Ewing's Tumour studies (ET-1 and ET-2). Patients have been followed for up to 20 years. These studies had suggested that better 5-year survival with ET-2 over the earlier ET-1 was achieved by replacing cyclophosphamide by ifosfamide and increasing the dose of doxorubicin in a four-drug chemotherapy regimen. The updated hazard ratio, stratified for metastatic status at diagnosis, of 0.39 (95% confidence interval 0.12-0.61) confirmed the advantage of the ET-2 regimen in terms of overall survival. Cure models, based on the Weibull distribution, suggested that factors for long-term survival in addition to presence of metastases were age, primary site of tumour and study. Modelling identified the proportion cured with the ET-2 protocol as best at 70% in those who are under 10 years with a nonpelvic primary site and without metastatic disease. This contrasts to only 13% cure in those with the corresponding adverse prognostic indicators. Additionally, the risk of death remains greatest but relatively constant over the first 2 years postdiagnosis, and then declines to a lower but constant value for the next 3 years before reaching the 'cure plateau' at about 5 years. This investigation suggests that 'cure' is possible for patients with Ewing's sarcoma. This is established at approximately 5 years post diagnosis and the proportion cured depends on the presence of metastases, pelvic site and age at diagnosis.

On the evolution of statistical methods as applied to clinical trials.

This paper describes how statistical methods have evolved in parallel with activities associated with randomized control trials. In particular we emphasize the pivotal role of two papers published in British Journal of Cancer, and the paper describing the Cox proportional hazards model. In addition, the importance of early papers on estimating the sample size required for trials is highlighted. Later developments including the increasing roles for competing risks, multilevel modelling and Bayesian methodologies are described. The interplay between computer software and statistical methodological developments is stressed. Finally some future directions are indicated.

Pilot study using technetium-99m pertechnetate sequential radionuclide-sialography to assess salivary gland function in nasopharyngeal cancer patients on radiation therapy.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is mainly treated by radiation therapy. A common complication of radiotherapy is xerostomia. Direct measurements of the amount of saliva produced using suction cups and volumetric assessments are cumbersome and time-consuming. Sequential radionuclide sialography is a reproducible and convenient method of measuring salivary function. MATERIALS AND METHODS: Patients with newly diagnosed NPC underwent a pilot study using technetium-99m pertechnetate sequential radionuclide sialography to assess their salivary function before and at 3 months post radiation therapy. From the sialography, time activity curves were obtained for analysis of salivary function. The shape of the time activity curve with citric acid stimulation was classified into 4 types according to the degree of radiation-induced dysfunction. RESULTS: All 14 patients had worse (P < 0.005) time activity curves for both parotids and submandibular glands after radiation therapy. All patients with abnormal curves before radiation therapy presented type IV (non-functioning) curve after radiation therapy. A ratio of pre- and post-stimulation counts allowed for quantification of the degree of stimulatory response. We found a significant decrease in Rc before and after radiation therapy for all salivary glands (P < 0.001). The salivary gland to background ratio, which is a reflection of the degree of salivary gland functional uptake, also had a significant reduction after radiation. CONCLUSION: It is feasible to use technetium-99m pertechnetate in the measurement of salivary gland function in nasopharyngeal cancer patients treated with radiation therapy.

Risk factors for nuclear, cortical and posterior subcapsular cataracts in the Chinese population of Singapore: the Tanjong Pagar Survey.

AIM: To describe risk factors for nuclear, cortical, and posterior subcapsular (PSC) cataracts in Chinese Singaporeans. METHODS: A population based cross sectional study was carried out on ethnic Chinese men and women aged 40-81 years. A stratified, clustered, disproportionate (more weights to older people), random sampling procedure was used to initially select 2000 Chinese names of those aged 40-79 years from the 1996 electoral register in the Tanjong Pagar district in Singapore. Eligible subjects (n = 1717) were invited for a standardised ocular examination and interview at a centralised clinic, following which an abbreviated examination was conducted for non-respondents in their homes. Cataract was graded clinically using to the Lens Opacity Classification System (LOCS) III system. The main outcome measures were adjusted odds ratio for risk factors for specific cataract types (nuclear, cortical and PSC), any cataract and cataract surgery, examined in multiple logistic regression models. RESULTS: Out of the 1232 (71.8%) examined, 1206 (70.2%) provided lens data for this analysis. Increasing age was associated with all cataract types, any cataract, and cataract surgery. There was no significant sex difference in presence of any cataract, specific cataract types or cataract surgery. After controlling for age, sex, and other factors, diabetes was associated with cortical cataract (3.1; 95% CI: 1.6 to 6.1), PSC cataract (2.2; 95% CI 1.2 to 4.1), any cataract (2.0; 95% CI: 0.9 to 4.5), and cataract surgery (2.3; 95% CI: 1.3 to 4.1). Lower body mass index was associated with cortical cataract (1.8; 95% CI: 1.1 to 2.9; lowest versus highest quintile) and any cataract (2.3; 95% CI: 1.3 to 4.0). Current cigarette smoking was associated with nuclear cataract (1.7, 95% CI: 1.0 to 2.9; more than 10 cigarettes per day versus none). A non-professional occupation was associated with nuclear cataract (2.9; 95% CI: 1.5 to 5.8; for production or machine operators and 2.6; 95% CI: 1.2 to 5.5; for labourers or agricultural workers, both versus professionals). Lower education was associated with nuclear cataract (2.3; 95% CI: 1.0 to 5.2, none versus tertiary), while lower household income was associated with PSC cataract (4.7, 95% CI: 1.1 to 20.0; income S$4000). CONCLUSIONS: Age related cataracts are associated with a variety of risk factors among Chinese people in Singapore, similar to those reported in European, Indian, and African derived populations. These data support common aetiological mechanisms for age related cataracts, irrespective of ethnic origin.

Angular regression and the detection of the seasonal onset of disease.

BACKGROUND: In examining the seasonality of onset of a disease over the year, investigators attempt to identify the peak of onset, and its magnitude. A second objective is to see if the day in which the disease manifests itself is related to subject-specific characteristics or environmental factors. METHOD: This paper describes appropriate statistical methodology for the situation where seasonality can be summarised by either a single peak or several peaks, possibly determined by patient characteristics or external influences. The circular, rather than linear, nature of the day of onset of a disease (irrespective of year) requires angular regression techniques to assess these relations, and the von Mises distribution replaces the normal distribution in this context. RESULTS: The methods outlined are illustrated by a national study of those experiencing an attack of acute primary angle-closure glaucoma in Singapore. CONCLUSIONS: We recommend re-analyses of already published work on seasonality of disease using this angular methodology. We anticipate that this may provide both useful further insight into aspects of aetiology and case studies for the methods themselves.

A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic nasopharyngeal cancer.

The Simon two-stage minimax design is a popular statistical design used in Phase II clinical trials. The analysis of the data arising from the design typically involves the use of frequentist statistics. This paper presents an alternative, Bayesian, approach to the design and analysis of Phase II clinical trials. In particular, we consider how a Bayesian approach could have affected the design, analysis and interpretation of two parallel Phase II trials of the National Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naïve and in previously treated patients with metastatic nasopharyngeal carcinoma. We begin by explaining the Bayesian methodology and contrasting it with the frequentist approach. We then carry out a Bayesian analysis of the trial results. The conclusions drawn using the Bayesian approach were in general agreement with those obtained from the frequentist analysis. However they had the advantage of allowing for different and potentially more useful interpretations to be made regarding the trial results, as well as for the incorporation of external sources of information. In particular, using a Bayesian trial design, we were able to take into account the results of the parallel trial results when deciding whether to continue each trial beyond the interim stage.