Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol

Introduction Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported. Hypothesis: Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.

Methods and analysis Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.

Ethics and dissemination The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r).

Both English and Latin: Bilingualism and Biculturalism in Milton's Neo-Latin Writings (219pp.)

Review by Emma A. Wilson, Milton Quarterly 49.1 (March, 2015), 54-59:

‘This volume provides an invaluable new perspective on both Milton’s neo-Latin poems and also the major vernacular poetry by insisting politely but firmly upon the bilingualism of their author and the manifest effects of that bilingualism upon style and intertextuality in his corpus. Through a dextrous combination of manuscript research, modern understandings of bilingualism, and crucially meticulous and demanding close readings, this volume succeeds in vivifying a wealth of new relationships between Milton’s neo-Latin works and his vernacular poems … Haan is expert in probing and elucidating the multiple linguistic and cultural lenses through which Milton projects his work, and the resulting volume brings a new set of historical contexts and consequences for both the major and minor texts, whilst also more importantly furnishing an exciting new method with which to approach these works as a whole ... Haan's linguistic expertise and meticulous archival research combine to create a critical work in which discoveries gradually accumulate and speak to one another in very specific, nuanced dialogues between chapters ... opening up exciting new reading vistas ... The final two chapters, in which Haan harvests some of the fruits of her considerable and fantastic labor in the archives and in current linguistic research into bilingualism, bring to light fresh perspectives on some of Milton's major published poetic works.’


Both English and Latin: Bilingualism and Biculturalism in Milton’s Neo-Latin Writings (2012) (Back Cover):

Gordon Campbell, University of Leicester:
‘Estelle Haan is the world’s foremost authority on Milton’s Latin poetry, and probably the most distinguished student of that poetry in the history of critical commentary. This is a work of extraordinary authority written by a scholar at the height of her powers. In short, this is a terrific book, elegant and informative.’

Anne Mahoney, Tufts University:
‘This book ssucceeds in presenting Milton's poetry as a single, unified body of work. Its biggest strength is the many close readings of Milton's Latin verse as engagements with classical Latin literature. In addition to introducing the Latin verse to new readers, it provides a new approach to Paradise Lost, one that accounts for one of the difficulties of Milton’s text—its language—in a novel way.’


Abstract:

Both English and Latin examines the interplay of Latin and English in a selection of John Milton's neo-Latin writings. It argues that this interplay is indicative of an inherent bilingualism that proceeds hand-in-hand with a self-fashioning that is bicultural in essence. Interlingual flexibility ultimately proved central to the poet of Paradise Lost, an epic uniquely characterized by its Latinate vernacular and its vernacular Latinitas.

'Neo-Latin Writing in the British Isles'

This chapter seeks to identify cultural and generic trends and authorial methodologies that may serve to unify or to differentiate between the histories of neo-Latin literature in England, Scotland, Wales and Ireland. It considers ways in which Latin served to bridge horizontal spaces (both physical and metaphorical) between four British regions, between neo-Latin writers in Britain and their continental predecessors and peers, and between Latin and the respective vernacular(s). It also examines vertical spaces (both chronological and cultural) between the neo-Latin and the classical Latin text, and between the linear demarcations of ‘early modern’, ‘Augustan’ and ‘Romantic’. An assessment of links between nationhood and the neo-Latin text as evinced by anthologies, antiquarian and quasi-historical writing, is followed by examples of generic continuity and metamorphosis in the British neo-Latin pastoral, ode and epigram. The concluding sections offer two generic case-studies (neo-Latin epic and didactic) both of which, it is argued, engendered the birth of specifically British versions of the mock-heroic and mock-didactic.

‘Proficiscere, anima Christiana’: Gerontius and German mysticism

The popularity in Britain of Elgar's _The Dream of Gerontius_ was triggered by the successful reception of the work in Germany in December 1901 and May 1902. By examining some of the writings on Elgar by German critics in this period, I explain that what may have particularly have appealed to German audiences was the composer's engagement with mysticism, something that as well as being a distinct strand of German theology since medieval times had acquired a new popularity among German artists in a number of fields as part of a reaction to the materialism of Wilhelmine Germany. Through a reading of the work that takes into account both its Catholic theology and ideas of mysticism more generally, I propose that the two Parts of the work should be conceived as taking place simultaneously, rather than successively, and that the work is thus best understood as belonging to the genre of epic rather than drama. ©2013 The Royal Musical Association

Home Is Where the Self Is: Monodrama, Journey-Play Structure, and the Modernist Fairy Tale

The first decade of the twentieth century witnessed the creation of two of the most beloved works of children’s literature ever produced. L. Frank Baum’s 1900 novel The Wizard of Oz and Maurice Maeterlinck’s 1908 play each gave rise to many adaptations, including, well beloved film versions, and both have become a deeply ingrained part of the cultural memory and construction of childhood in both Europe and the United States. And while these works are deeply original in content and detail, the structure of these works harkens back to the form of the journey play (traceable, on some level, back to the medieval morality play Everyman), a form that had undergone a considerable revival in the second half of the nineteenth century in the work of writers such as Henrik Ibsen and August Strindberg. This article explores the structural and conceptual links between Baum and Maeterlinck’s children’s classics, Ibsen’s Norwegian folk play Peer Gynt, and August Strindberg’s Lucky Per’s Journey and The Road to Damascus, Part I. In these works, the protagonists, disenchanted with their homes or current situations, set out on an epic journey in which they come upon characters and situations that act as commentary upon their situations before the journey. Ultimately, the characters return to where they started, with the journey seeming to have been a dream or merely a pointless excursion. But in these journeys of self-discovery, the protagonist that emerges at the end has undergone a significant transformation, a process at the heart of all of these works.

The DietCompLyf study: A prospective cohort study of breast cancer survival and phytoestrogen consumption

DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.

Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial.

METHODS: The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry, number ISRCTN97182923.

FINDINGS: 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4-64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (<1%), three (<1%) and three (<1%) men respectively (74 Gy vs 60 Gy, ptrend=0.64, 74 Gy vs 57 Gy, ptrend=0·59). We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months.

INTERPRETATION: The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Do exoplanets spin up their host stars?

We have collected initial evidence that tidal interaction between a late-type star and its close-in, massive planet can lead to a spin-up of the host star. We propose to explore this further by studying a small sample of proper motion pairs in which one of the stars is orbited by a Hot Jupiter. We will determine if the activity-estimated age appears to be strongly different for the two stars, which would indicate a tidal spin up of the Hot Jupiter host star. We propose to observe 4 such systems with Chandra/ACIS-S, and to perform a similar observation of one additional system with large angular separation using XMM-Newton/EPIC. The total proposed exposure times are 141 ks (Chandra) and 38 ks (XMM).