Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer

Background: The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. Results: In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis, and the rate was lower in the interferon β-1b group. Then all subjects were offered interferon β-1b, and the original interferon β-1b group became the early treatment group, and the placebo group became the delayed treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early treatment than late treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Conclusions: Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.26 to 0.64 cm, for the MLC, from 0.12 to 0.43 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

The importance of accurate beam data measurement for SRT/SRS treatment planning

Introduction This study investigated the sensitivity of calculated stereotactic radiotherapy and radiosurgery doses to the accuracy of the beam data used by the treatment planning system. Methods Two sets of field output factors were acquired using fields smaller than approximately 1 cm2, for inclusion in beam data used by the iPlan treatment planning system (Brainlab, Feldkirchen, Germany). One set of output factors were measured using an Exradin A16 ion chamber (Standard Imaging, Middleton, USA). Although this chamber has a relatively small collecting volume (0.007 cm3), measurements made in small fields using this chamber are subject to the effects of volume averaging, electronic disequilibrium and chamber perturbations. The second, more accurate, set of measurements were obtained by applying perturbation correction factors, calculated using Monte Carlo simulations according to a method recommended by Cranmer-Sargison et al. [1] to measurements made using a 60017 unshielded electron diode (PTW, Freiburg, Germany). A series of 12 sample patient treatments were used to investigate the effects of beam data accuracy on resulting planned dose. These treatments, which involved 135 fields, were planned for delivery via static conformal arcs and 3DCRT techniques, to targets ranging from prostates (up to 8 cm across) to meningiomas (usually more than 2 cm across) to arterioveinous malformations, acoustic neuromas and brain metastases (often less than 2 cm across). Isocentre doses were calculated for all of these fields using iPlan, and the results of using the two different sets of beam data were evaluated. Results While the isocentre doses for many fields are identical (difference = 0.0 %), there is a general trend for the doses calculated using the data obtained from corrected diode measurements to exceed the doses calculated using the less-accurate Exradin ion chamber measurements (difference\0.0 %). There are several alarming outliers (circled in the Fig. 1) where doses differ by more than 3 %, in beams from sample treatments planned for volumes up to 2 cm across. Discussion and conclusions These results demonstrate that treatment planning dose calculations for SRT/SRS treatments can be substantially affected when beam data for fields smaller than approximately 1 cm2 are measured inaccurately, even when treatment volumes are up to 2 cm across.

Potential role of EPB41L3 (Protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer

Background: Loss of erythrocyte membrane protein band 4.1-like 3 (EPB41L3; aliases: protein 4.1B, differentially expressed in adenocarcinoma of the lung-1 (Dal-1)) expression has been implicated in tumor progression. Objective: To evaluate literature describing the role of EPB41L3 in tumorigenesis and metastasis, and to consider whether targeting this gene would be useful in the treatment of prostate cancer. Methods: A literature review of studies describing EPB41L3 and its aliases was conducted. Online databases (NCBI, SwissProt) were also interrogated to collect further data. Results/conclusion: A growing body of evidence supports a role for loss of EPB41L3 in tumor progression, including in prostate cancer. Therapeutic strategies that could be harnessed to upregulate EPB41L3 gene expression in prostate cancer cells are currently being developed.

A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.

I-cobb - An innovative technique in spinal radiographic measurement

The measurement of Cobb angles on radiographs of patients with spinal deformities is routine practice in spinal clinics. The technique relies on the use and availability of specialist equipment such as a goniometer, cobbometer or protractor. The aim of this study was to validate the use of i-Phone (Apple Inc) combined with Tilt Meter Pro software as compared to a protractor in the measurement of Cobb angles. The i-Phone combined with Tilt Meter Pro software offers a faster alternative to the traditional method of Cobb angle measurement. The use of i-Phone offers a more convenient way of measuring Cobb angles in the outpatient setting. The intra-observer repeatability of the iPhone is equivalent to the protractor in the measurement of Cobb angles.

The relationship between deformity correction and clinical outcomes after thoracoscopic scoliosis surgery

Surgical treatment of scoliosis is quantitatively assessed in the clinic using radiographic measures of deformity correction, as well as the rib hump, but it is important to understand the extent to which these quantitative measures correlate with self-reported improvements in patients’ quality of life following surgery. The purpose of this prospective study was to evaluate the relationship between clinical outcomes of thoracoscopic anterior scoliosis surgery and deformity correction using the Scoliosis Research Society questionnaire (SRS-24). Patients undergoing thoracoscopic anterior scoliosis correction report good SRS scores which are comparable to those reported in previous studies for both open and thoracoscopic scoliosis correction procedures. Major Cobb correction is a significant predictor of patient satisfaction when comparing subgroups of patients with the highest and lowest major curve corrections.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Telcagepant is a new oral treatment for migraine

Background : Migraine is a common cause of disability. Many subjects (30 – 40%) do not respond to the 5-HT 1B/1D agonists (the triptans) commonly used in the treatment of migraine attacks. Calcitonin gene-related protein (CGRP) receptor antagonism is a new approach to the treatment of migraine attacks. Objectives/methods : This evaluation is of a Phase III clinical trial comparing telcagepant, an orally active CGRP receptor antagonist, with zolmitriptan in subjects during an attack of migraine. Results : Telcagepant 300 mg has a similar efficacy to zolmitriptan in relieving pain, phonophobia, photophobia, and nausea. Telcagepant was better tolerated than zolmitriptan. Conclusions : The initial Phase III clinical trial results with telcagepant are promising but several further clinical trials are needed to determine the place of telcagepant in the treatment of migraine attacks

The creative sector in New Zealand : mapping and economic role : report to New Zealand Trade and Enterprise

The New Zealand creative sector was responsible for almost 121,000 jobs at the time of the 2006 Census (6.3% of total employment). These are divided between • 35,751 creative specialists – persons employed doing creative work in creative industries • 42,300 support workers - persons providing management and support services in creative industries • 42,792 embedded creative workers – persons engaged in creative work in other types of enterprise The most striking feature of this breakdown is the fact that the largest group of creative workers are employed outside the creative industries, i.e. in other types of businesses. Even within the creative industries, there are fewer people directly engaged in creative work than in providing management and support. Creative sector employees earned incomes of approximately $52,000 per annum at the time of the 2006 Census. This is relatively uniform across all three types of creative worker, and is significantly above the average for all employed persons (of approximately $40,700). Creative employment and incomes were growing strongly over both five year periods between the 1996, 2001 and 2006 Censuses. However, when we compare creative and general trends, we see two distinct phases in the development of the creative sector: • rapid structural growth over the five years to 2001 (especially led by developments in ICT), with creative employment and incomes increasing rapidly at a time when they were growing modestly across the whole economy; • subsequent consolidation, with growth driven by more by national economic expansion than structural change, and creative employment and incomes moving in parallel with strong economy-wide growth. Other important trends revealed by the data are that • the strongest growth during the decade was in embedded creative workers, especially over the first five years. The weakest growth was in creative specialists, with support workers in creative industries in the middle rank, • by far the strongest growth in creative industries’ employment was in Software & digital content, which trebled in size over the decade Comparing New Zealand with the United Kingdom and Australia, the two southern hemisphere nations have significantly lower proportions of total employment in the creative sector (both in creative industries and embedded employment). New Zealand’s and Australia’s creative shares in 2001 were similar (5.4% each), but in the following five years, our share has expanded (to 5.7%) whereas Australia’s fell slightly (to 5.2%) – in both cases, through changes in creative industries’ employment. The creative industries generated $10.5 billion in total gross output in the March 2006 year. Resulting from this was value added totalling $5.1b, representing 3.3% of New Zealand’s total GDP. Overall, value added in the creative industries represents 49% of industry gross output, which is higher than the average across the whole economy, 45%. This is a reflection of the relatively high labour intensity and high earnings of the creative industries. Industries which have an above-average ratio of value added to gross output are usually labour-intensive, especially when wages and salaries are above average. This is true for Software & Digital Content and Architecture, Design & Visual Arts, with ratios of 60.4% and 55.2% respectively. However there is significant variation in this ratio between different parts of the creative industries, with some parts (e.g. Software & Digital Content and Architecture, Design & Visual Arts) generating even higher value added relative to output, and others (e.g. TV & Radio, Publishing and Music & Performing Arts) less, because of high capital intensity and import content. When we take into account the impact of the creative industries’ demand for goods and services from its suppliers and consumption spending from incomes earned, we estimate that there is an addition to economic activity of: • $30.9 billion in gross output, $41.4b in total • $15.1b in value added, $20.3b in total • 158,100 people employed, 234,600 in total The total economic impact of the creative industries is approximately four times their direct output and value added, and three times their direct employment. Their effect on output and value added is roughly in line with the average over all industries, although the effect on employment is significantly lower. This is because of the relatively high labour intensity (and high earnings) of the creative industries, which generate below-average demand from suppliers, but normal levels of demand though expenditure from incomes. Drawing on these numbers and conclusions, we suggest some (slightly speculative) directions for future research. The goal is to better understand the contribution the creative sector makes to productivity growth; in particular, the distinctive contributions from creative firms and embedded creative workers. The ideas for future research can be organised into the several categories: • Understanding the categories of the creative sector– who is doing the business? In other words, examine via more fine grained research (at a firm level perhaps) just what is the creative contribution from the different aspects of the creative sector industries. It may be possible to categorise these in terms of more or less striking innovations. • Investigate the relationship between the characteristics and the performance of the various creative industries/ sectors; • Look more closely at innovation at an industry level e.g. using an index of relative growth of exports, and see if this can be related to intensity of use of creative inputs; • Undertake case studies of the creative sector; • Undertake case studies of the embedded contribution to growth in the firms and industries that employ them, by examining taking several high performing noncreative industries (in the same way as proposed for the creative sector). • Look at the aggregates – drawing on the broad picture of the extent of the numbers of creative workers embedded within the different industries, consider the extent to which these might explain aspects of the industries’ varied performance in terms of exports, growth and so on. • This might be able to extended to examine issues like the type of creative workers that are most effective when embedded, or test the hypothesis that each industry has its own particular requirements for embedded creative workers that overwhelms any generic contributions from say design, or IT.

The relationship between deformity correction and clinical outcomes after thoracoscopic scoliosis surgery : a prospective series of 100 patients

The relationship between deformity correction and self-reported patient satisfaction after thoracoscopic anterior scoliosis surgery is unknown. Scoliosis Research Society questionnaire scores, radiographic outcomes, and rib hump correction were prospectively assessed for a group of 100 patients pre-operatively and at two years after surgery. Patients with lower post-op major Cobb angles report significantly higher SRS scores than patients with higher post-op Cobb angles.

The relationship between deformity correction and clinical outcomes after thoracoscopic scoliosis surgery : a prospective series of one hundred patients

Prospective clinical case series of 100 patients receiving thoracoscopic anterior scoliosis correction surgery. The objective was to evaluate the relationship between clinical outcomes of thoracoscopic anterior scoliosis surgery and deformity correction using the Scoliosis Research Society (SRS) outcomes instrument questionnaire. The surgical treatment of scoliosis is quantitatively assessed in the clinic using radiographic measures of deformity correction, as well as the rib hump, but it is important to understand the extent to which these quantitative measures correlate with self-reported improvements in patients’ quality of life following surgery. A series of 100 consecutive adolescent idiopathic scoliosis patients received a single anterior rod via a thoracoscopic approach at the Mater Children’s Hospital, Brisbane, Australia. Patients completed SRS outcomes questionnaires pre-operatively and at 24 months post-operatively. There were 94 females and 6 males with a mean age of 16.1 years. The mean Cobb angle improved from 52º pre-operatively to 25º post-operatively (52%) and the mean rib hump improved from 16º to 8º (51%). The mean total SRS score for the cohort was 99.4/120. None of the deformity related parameters in the multiple regression were significant. However, patients with the lowest post-operative major Cobb angles reported significantly higher SRS scores than those with the highest post-operative Cobb angles, but there was no difference on the basis of rib hump correction. There were no significant differences between patients with either rod fractures or screw-related complications compared to those without complications.

Functional status, postural stability and falls among older adults with glaucoma

Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.

Interaction of NPR1 with basic leucine zipper protein transcription factors that bind sequences required for salicylic acid induction of the PR–1 gene

The Arabidopsis thaliana NPR1 has been shown to be a key regulator of gene expression during the onset of a plant disease-resistance response known as systemic acquired resistance. The npr1 mutant plants fail to respond to systemic acquired resistance-inducing signals such as salicylic acid (SA), or express SA-induced pathogenesis-related (PR) genes. Using NPR1 as bait in a yeast two-hybrid screen, we identified a subclass of transcription factors in the basic leucine zipper protein family (AHBP-1b and TGA6) and showed that they interact specifically in yeast and in vitro with NPR1. Point mutations that abolish the NPR1 function in A. thaliana also impair the interactions between NPR1 and the transcription factors in the yeast two-hybrid assay. Furthermore, a gel mobility shift assay showed that the purified transcription factor protein, AHBP-1b, binds specifically to an SA-responsive promoter element of the A. thaliana PR-1 gene. These data suggest that NPR1 may regulate PR-1 gene expression by interacting with a subclass of basic leucine zipper protein transcription factors.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.