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The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom). Data on invasive EOC diagnosed in women aged 15-99 years during 1995-2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group, and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995-2014 among women aged 65-99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma 'not otherwise specified' with estimates ranging between 4.4% and 7.4% in women aged 15-64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival. This article is protected by copyright. All rights reserved.

BACKGROUND: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8. Here, we present the final coprimary outcomes of overall survival and updated progression-free survival analyses of ICON8. METHODS: In this open-label, randomised, controlled, phase 3 trial (ICON8), women aged 18 years or older with newly diagnosed stage IC-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (here collectively termed ovarian cancer, as defined by International Federation of Gynecology and Obstetrics [FIGO] 1988 criteria) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 117 hospitals with oncology departments in the UK, Australia and New Zealand, Mexico, South Korea, and Ireland. Patients could enter the trial after immediate primary surgery (IPS) or with planned delayed primary surgery (DPS) during chemotherapy, or could have no planned surgery. Participants were randomly assigned (1:1:1), using the Medical Research Council Clinical Trials Unit at University College London randomisation line with stratification by Gynecologic Cancer Intergroup group, FIGO disease stage, and outcome and timing of surgery, to either 3-weekly carboplatin area under the curve (AUC)5 or AUC6 and 3-weekly paclitaxel 175 mg/m2 (control; group 1), 3-weekly carboplatin AUC5 or AUC6 and weekly paclitaxel 80 mg/m2 (group 2), or weekly carboplatin AUC2 and weekly paclitaxel 80 mg/m2 (group 3), all administered via intravenous infusion for a total of six 21-day cycles. Coprimary outcomes were progression-free survival and overall survival, with comparisons done between group 2 and group 1, and group 3 and group 1, in the intention-to-treat population. Safety was assessed in all patients who started at least one chemotherapy cycle. The trial is registered on ClinicalTrials.gov, NCT01654146, and ISRCTN registry, ISRCTN10356387, and is closed to accrual. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 patients were randomly assigned to group 1 (n=522), group 2 (n=523), or group 3 (n=521). The median age was 62 years (IQR 54-68), 1073 (69%) of 1566 patients had high-grade serous carcinoma, 1119 (71%) had stage IIIC-IV disease, and 745 (48%) had IPS. As of data cutoff (March 31, 2020), with a median follow-up of 69 months (IQR 61-75), no significant difference in overall survival was observed in either comparison: median overall survival of 47·4 months (95% CI 43·1-54·8) in group 1, 54·8 months (46·6-61·6) in group 2, and 53·4 months (49·2-59·6) in group 3 (group 2 vs group 1: hazard ratio 0·87 [97·5% CI 0·73-1·05]; group 3 vs group 1: 0·91 [0·76-1·09]). No significant difference was observed for progression-free survival in either comparison and evidence of non-proportional hazards was seen (p=0·037), with restricted mean survival time of 23·9 months (97·5% CI 22·1-25·6) in group 1, 25·3 months (23·6-27·1) in group 2, and 24·8 months (23·0-26·5) in group 3. The most common grade 3-4 adverse events were reduced neutrophil count (78 [15%] of 511 patients in group 1, 183 [36%] of 514 in group 2, and 154 [30%] of 513 in group 3), reduced white blood cell count (22 [4%] in group 1, 80 [16%] in group 2, and 71 [14%] in group 3), and anaemia (26 [5%] in group 1, 66 [13%] in group 2, and 24 [5%] in group 3). No new serious adverse events were reported. Seven treatment-related deaths were reported (two in group 1, four in group 2, and one in group 3). INTERPRETATION: In our cohort of predominantly European women with epithelial ovarian cancer, we found that first-line weekly dose-dense chemotherapy did not improve overall or progression-free survival compared with standard 3-weekly chemotherapy and should not be used as part of standard multimodality front-line therapy in this patient group. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

Supplemental Figure I. Homology modelling of the Ad5NULL-A20 complex; Supplement II. Biodistribution study: Heat-map images of luminescence intensity ex vivo; Supplement II. Biodistribution study: Immunohistochemistry on formalin-fixed, paraffinembedded liver sections; Supplementary Figure IV. Pilot study: Tumour localisation and take rate in NOD/SCID mice; Supplement II. Biodistribution study: Immunohistochemistry on formalin-fixed, paraffinembedded; liver sections; Supplementary Figure IV. Pilot study: Tumour localisation and take rate in NOD/SCID mice.

Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for the manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumor-selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but nondetectable in healthy tissues.Experimental Design: Ad5NULL-A20 harbors mutations in each major capsid protein to preclude uptake via all native pathways. Tumor-tropism via αvβ6 targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed.Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins, and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of preexisting anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non–tumor-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared with Ad5. Tumor uptake, transgene expression, and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20–treated animals demonstrated significantly improved survival compared with those treated with oncolytic Ad5.Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-overexpressing cancers and exciting platforms for tumor-selective overexpression of therapeutic anticancer modalities, including immune checkpoint inhibitors. Clin Cancer Res; 24(17); 4215–24. ©2018 AACR.

OBJECTIVE To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing. DESIGN National retrospective audit. SETTING The All Wales Medical Genomics Service (AWMGS). POPULATION Patients with high-grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS. METHODS Analysis of NGS data from germline and/or tumour testing. MAIN OUTCOME MEASURES Frequency of BRCA1 and BRCA2 pathogenic variants. RESULTS The overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone. CONCLUSIONS Parallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high-grade serous ovarian cancer. TWEETABLE ABSTRACT Parallel germline and tumour testing maximises BRCA pathogenic variant detection in ovarian cancer.

The attitudes of student-teachers to Computer Assisted Language Learning (CALL) remains an under-explored topic in research literature. This mixed-methods study engaged student-teachers in focus group discussions at commencement and completion of Initial Teacher Education (ITE). These student-teachers were situated across England, Scotland, Wales, and Northern Ireland. Student-teachers’ beliefs regarding the perceived value of CALL experienced a considerable transformation between initial and follow-up focus group interactions. Beginning student-teachers collectively portrayed CALL in a complimentary light, with 67.5% of participant dialogue positively coded via thematic analysis. This contrasts with follow-up student-teacher discourse, where only 38.55% of nodes in NVivo were positively coded. Overall, belief changes were most marked for positive categories of CALL. Thus, maintaining optimistic opinions to CALL could be a worthwhile endeavour to promote student-teacher acceptance of digital technologies in language learning.

A study was carried out with 33 teachers of Modern Foreign Languages (MFL) to obtain information on the interaction of classroom professionals with Computer Assisted Language Learning (CALL) and digital technologies in Second Language (L2) education. MFL teachers were recruited through Facebook groups in the UK. Research subjects were asked to fill out a questionnaire with CALL-specific statements. Significantly, participants recognised a gap in practice versus the expectation of CALL in the MFL classroom. Overall, participants were shown to be interested adopted and daily users of CALL who appreciated its ease and importance for teaching and learning in L2 pedagogy.

This is the fourth and final article in a series on the gastrointestinal (GI) symptoms of pelvic radiation disease (PRD). Published studies and patient reports suggest that health professionals lack of awareness of PRD. This professional awareness can be improved with third-sector advocacy and provision of simple screening tools, such as Assessment of Late Effects of Radiotherapy-Bowel (ALERT-B). In South Wales, patients with suspected PRD are referred to a PRD specialist nurse in either a gastroenterology clinic or a gynae-oncology follow-up clinic. These two nurse-led clinics demonstrate different ways to identify, assess and manage patients with late GI effects of PRD. Data from these clinics suggest that systematic investigations based on appropriate guidance are effective in identifying these symptoms, many of which can be managed or treated. The rising incidence of PRD and lack of specialist services suggests that the NHS needs to provide more funding to care for patients beyond the end of their cancer treatment.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries.METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach.RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway).CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

A study was performed with 33 Modern Foreign Language (MFL) teachers to afford insight into how classroom practitioners interact with Computer Assisted Language Learning (CALL) in Second Language (L2) pedagogy. A questionnaire with CALL specific statements was completed by MFL teachers who were recruited via UK based Facebook groups. Significantly, participants acknowledged a gap in practice from the expectation of CALL in the MFL classroom. Overall, respondents were shown to be interested and regular consumers of CALL who perceived its ease and importance in L2 teaching and learning.

Anthracycline chemotherapy administered via a peripheral cannula results in severe anthracycline chemotherapy-induced phlebitis (ACIP) in about 20-30% of patients. Administering chemotherapy via a central venous catheter (CVC) prevents ACIP. However, CVCs are associated with an increased risk of thrombosis and sepsis. Our aim was to identify risk factors associated with severe ACIP and to provide evidence about the individual risk of developing symptoms.A prospective observational study of 263 women with breast cancer receiving peripheral administration of anthracycline chemotherapy at a UK cancer centre was conducted between May 2016 and January 2018. Data were collected at baseline and every 3 weeks following each chemotherapy treatment, using both healthcare professional- and participant-reported symptom assessments.After three cycles of chemotherapy, 27% of participants experienced severe ACIP. Factors associated with symptom severity were identified as: arm used for chemotherapy administration, epirubicin dose, age, pre-existing hypertension, comorbidity, ethnic group and pain during chemotherapy administration. The sequence of arm used for chemotherapy administration was the single most significant factor (P0.001). When alternating arms were used no other risk factor was influential. Where alternating arms were not used, younger age and higher dose were associated with higher-grade symptoms, with age being more influential than dose. The cumulative effect of increasing symptom severity with repeated cycles was also identified (P0.001).It is recommended that a CVC is not routinely required for women with breast cancer who have not undergone an axillary node clearance and receive chemotherapy in alternate arms. The need for a CVC for women who are planned to receive all anthracycline chemotherapy cycles in the same arm should be assessed in the light of peripheral venous access assessment and the key risk factors of age, dose and number of cycles.

Aims Pelvic radiotherapy adds significantly to the curative treatment of many pelvic malignancies. However, this cure comes at a cost for many patients, where late bowel toxicities, such as faecal incontinence, urgency and diarrhoea, adversely affect quality of life. Despite the implementation of advanced radiotherapy techniques in many centres, there are deficiencies in our knowledge of how to make best use of these techniques to minimise these late toxicities, with dose–volume constraints specifically for late effects needing definition. The aims of this study were to establish dose–volume predictors for patient-reported late bowel toxicities and derive constraints for clinical use to reduce the risk of these toxicities. Materials and methods All radiotherapy patients treated in our institution between 2012 and 2014 for gynaecological and urological cancers (bladder, prostate where pelvic nodes are treated) were identified. Patients were sent patient-reported toxicity questionnaires at 12 and 24 months after treatment. Planning computed tomography scans were retrospectively contoured with different definitions of bowel as organs at risk (OARs). Dose–volume data for each OAR were collected and predictors of these toxicities found using multivariate analysis. For those dose–volume predictors found to be significant on multivariate analysis, statistically significant and clinically relevant dose–volume constraints were derived. Furthermore, data collected were used to validate constraints from published studies. Results Faecal urgency, incontinence and diarrhoea rates were found in 52, 23.5 and 18.7% of the 203 patients included at 12 months following radiotherapy. Dose–volume parameters for sigmoid colon and large bowel were significant for these toxicities, and constraints for these OARs were derived, which are promising. A previously published constraint for bowel loops was validated with our data. Conclusions The sigmoid colon and large bowel are important OARs for the development of faecal urgency, incontinence and diarrhoea. Promising constraints for these OARs were derived, which require further validation before prospective clinical use.

IntroductionThe International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65–74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities.ObjectiveTo compare clinical practice guidelines and patterns of care across seven high-income countries.MethodsA comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by ‘distant’ stage using Spearman’s rho.ResultsTwenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/‘ultra-radical’ surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits.DiscussionFindings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for the manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumor-selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but nondetectable in healthy tissues. Experimental Design: Ad5NULL-A20 harbors mutations in each major capsid protein to preclude uptake via all native pathways. Tumor-tropism via αvβ6 targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed. Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins, and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of preexisting anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non–tumor-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared with Ad5. Tumor uptake, transgene expression, and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20–treated animals demonstrated significantly improved survival compared with those treated with oncolytic Ad5. Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-overexpressing cancers and exciting platforms for tumor-selective overexpression of therapeutic anticancer modalities, including immune checkpoint inhibitors. Clin Cancer Res; 24(17); 4215–24. ©2018 AACR.

Introduction/Background Patients who receive pelvic radiotherapy may develop gastrointestinal (GI) symptoms which impact on their quality of life (QoL). A GI Specialist Nurse (CNS) has attended our gynaecological follow up clinic since January 2018. This is a new service in addition to a Late GI Effects Clinic based in the local Gastroenterology Department. Methodology From January 2018 to March 2019, 185 patients had received pelvic radiotherapy. 35% (65) of patients with GI symptoms were identified using the ALERT-B (Taylor et al 2016), a quick and simple screening tool. Those who answered yes to any question were seen by the GI CNS and investigated using the ‘Guidance: The Practical Management of Gastrointestinal Symptoms of Pelvic Radiation Disease’ (Andreyev et al 2014). Results Some of the 65 patients had also previously been investigated in the main Late Effects Clinic. The most common findings are shown in table 1 below. Many patients reported more than one symptom. Table 2 below shows the most common abnormal investigation results It was also identified that 22% (14) of patients required specialist dietary advice including certain carbohydrate avoidance, low fat and/or a low FODMAP diet. Conclusion Late GI effects are not uncommon following pelvic radiotherapy and can have a significant impact on the patients QoL. A GI Late Effects CNS in a gynaeoncology follow-up clinic quickly identifies, investigates and treats affected patients thus avoiding further clinic referral and speeding up the patients recovery. Disclosure Nothing to disclose

OBJECTIVE To establish whether using alternating arms for peripheral intravenous epirubicin administration affects the severity or duration of epirubicin-induced phlebitis. METHODS An observational study of women with breast cancer (n = 237) in a UK Cancer Centre. Data were analysed after receiving three treatment cycles according to the arm used for epirubicin administration: same, alternating or mixed arm (two consecutive cycles in one arm and one in the alternate arm). Phlebitis severity was graded by clinical staff after each treatment; participants also self-reported symptoms during treatment and for up to 6 months after. RESULTS The alternating arm group experienced significantly less severe symptoms than the other arm use groups, 6% (4 of 64) compared with 34% (p

Background\ud\udAdvanced pelvic radiotherapy techniques aim to reduce late bowel toxicity which can severely impact the lives of pelvic cancer survivors. Although advanced techniques have been largely adopted worldwide, to achieve their aim, knowledge of which dose-volume parameters of which components of bowel predict late bowel toxicity is crucial to make best use of these techniques.\ud\udThe rectum is an extensively studied organ at risk (OAR), and dose-volume predictors of late toxicity for the rectum are established. However, for other components of bowel, there is a significant paucity of knowledge. The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) reviews recommend dose-volume constraints for acute bowel toxicity for peritoneal cavity and bowel loops, although no constraints are recommended for late toxicity, despite its relevance to our increasing number of survivors. This systematic review aims to examine the published literature to seek dose-volume predictors and constraints of late bowel toxicity for OARs (apart from the rectum) for use in clinical practice.\ud\ud\udMethods\ud\udA systematic literature search was performed using Medline, Embase, Cochrane Library, Web of Science, Cinahl and Pubmed. Studies were screened and included according to specific pre-defined criteria. Included studies were assessed for quality against QUANTEC-defined assessment criteria.\ud\ud\udResults\ud\ud101 studies were screened to find 30 relevant studies. Eight studies related to whole bowel, 11 to small bowel, and 21 to large bowel (including 16 of the anal canal). The anal canal is an important OAR for the development of late toxicity, and we recommend an anal canal Dmean

Aims: Although pelvic radiotherapy is an effective treatment for various malignancies, around half of patients develop significant gastrointestinal problems. These symptoms often remain undetected, despite the existence of effective treatments. This study developed and refined a simple screening tool to detect common gastrointestinal symptoms in outpatient clinics. These symptoms have a significant effect on quality of life. This tool will increase detection rates and so enable access to specialist gastroenterologists, which will in turn lead to improved symptom control and quality of life after treatment. Materials and methods: A literature review and expert consensus meeting identified four items for the ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) screening tool. ALERT-B was face tested for its usability and acceptability using cognitive interviews with 12 patients experiencing late gastrointestinal symptoms after pelvic radiotherapy. Thematic analysis and probe category were used to analyse interview transcripts. Interview data were presented to a group of experts to agree on the final content and format of the tool. ALERT-B was assessed for reliability and tested for validity against the Gastrointestinal Symptom Rating Scale in a clinical study (EAGLE). Results: Overall, the tool was found to be acceptable in terms of wording, response format and completion time. Participant-reported experiences, including lifestyle modifications and the psychological effect of the symptoms, led to further modifications of the tool. The refined tool includes three questions covering rectal bleeding, incontinence, nocturnal bowel movements and impact on quality of life, including mood, relationships and socialising. ALERT-B was successfully validated against the Gastrointestinal Symptom Rating Scale in the EAGLE study with the tool shown broadly to be internally consistent (Cronbach’s alpha=0.61 and all item-subscale correlation [Spearman] coefficients are > 0.6). Conclusion: The ALERT-B screening tool can be used in clinical practice to improve post-treatment supportive care by triggering the clinical assessment of patients suitable for referral to a gastroenterologist.

Aims To seek the views of consultants appointed less than 2 years ago on the appropriateness of their training in fitting them to carry out their present posts, the FRCR examination, experience of research and the prevalence and value of out of programme experience and acting up as a consultant. Materials and methods All the consultants identified from the Royal College of Radiologists' database as having been appointed to a consultant post in the last 2 years were emailed inviting them to take part in a web-based survey. Results The response rate was 60% (32 of 53 consultants). Ninety-four per cent agreed or strongly agreed that training had equipped them for clinical work as a consultant, but only 44% agreed or strongly agreed that training had equipped them to fulfil the management roles. Free text answers stressed the importance of management skills, getting involved with trial set-up and producing publications early in their career. Ninety-four per cent agreed or strongly agreed that they had adequate opportunity to develop skills in systemic therapy and radiotherapy planning, but only 56% thought this was the case for intensity-modulated radiotherapy and image-guided radiotherapy. Although 87% agreed or strongly agreed they had sufficient opportunity to develop teaching skills, this was only the case in 62% with regard to research skills. They published a median number of three papers in peer-reviewed journals. Twenty-five per cent of respondents studied for research degrees; 69% of consultants had undertaken out of programme experience and 50% had acted up as a consultant and these were generally found to be valuable experiences. There was strong support for the FRCR examination. Conclusions Consultants appointed in the last 2 years are generally satisfied with their training. Training in intensity-modulated radiotherapy and image-guided radiotherapy should be improved and the advanced specialist training requires reviewing to better fit consultants for subspecialisation, management and research.

Purpose To assess the clinical outcomes after concurrent cisplatin chemotherapy and radiotherapy (RT) followed by high-dose-rate brachytherapy for locally advanced carcinoma of the cervix and perform a multivariate analysis of the prognostic factors. Methods and Materials The outcomes were analyzed for all women treated between 1999 and 2004 with concurrent cisplatin chemotherapy and RT followed by high-dose-rate brachytherapy. Kaplan-Meier analysis was used for overall survival (OS), local control (LC), and distant control (DC). The Cox proportional hazards model was used to perform multivariate analysis of the prognostic variables. Results The standard regimen comprised whole pelvic external RT 45 Gy in 25 fractions with concurrent weekly cisplatin 40 mg/m 2 , followed by four high-dose-rate brachytherapy insertions of 6 Gy. Patients with radiologically enlarged para-aortic lymph nodes underwent extended-field RT. Of 92 patients, the OS rate was 72% at 2 years and 55% at 5 years. The LC rate was 76% at 2 years and 67% at 5 years. The DC rate was 68% at 2 years and 48% at 5 years. The most important prognostic factor for OS, LC, and DC was the pretreatment hemoglobin. For OS, the tumor size and the presence of enlarged lymph nodes were also important. For LC, the number of brachytherapy insertions was important; and for DC, the number of chemotherapy treatments was important. Of the patients, 4% experienced late Grade 3 or 4 toxicity. Conclusion The results of our study have shown that the regimen is effective, with acceptable long-term side effects. In this cohort, the most important prognostic factor was the pretreatment hemoglobin level, a disease-related factor. However, more effective systemic treatments are needed.

Introduction It is important to understand the basic techniques of radiotherapy planning because these will help when developing complex plans. These techniques, which are taught at the First FRCR level (Royal College of Radiologists), are used by the treatment centre's Physics Department for checking the validity of calculations before they are applied to patients, and anyone interpreting plans will need to be familiar with them to know whether it is worth adjusting treatment plans during review. Advanced radiotherapy techniques will be discussed in Chapter 6. There are several useful reviews of radiotherapy physics in the literature. One by Shiu and Mellenberg (2001) includes sections on isodose planning. Another, by Purdy (2000), provides a perspective on future directions in 3D treatment planning. Radiotherapy is a rapidly developing field and it is important to ensure that new methods satisfy safety and effectiveness requirements before being adopted as routine treatments. This chapter will deal with the general principles of developing isodose plans that are suitable for treatment and will use specific examples to highlight particular points. It will focus mainly on external beam radiotherapy with megavoltage photons; there will be shorter sections on the use of electrons and brachytherapy. Some aspects of radiotherapy planning using lower energy (kilovoltage) photons will be discussed in Chapter 36. The use of unsealed radiation sources for prostate, thyroid and childhood cancers are discussed in Chapters 22, 38 and 40, respectively. Treatment planning overview Radiotherapy planning can be divided into stages as follows. • Patient preparation, position and immobilisation. • Localisation method (e.g. orthogonal films, CT scanning, and image co-registration). • Definition of target volumes and organs at risk. • Radiotherapy technique, including beam arrangements, beam energy, size and shape, weighting, wedges and production of isodose plan. • Prescription, including number of phases, dose, energy and fractionation. • Verification (i.e. checking the geometrical set-up of the treatment). This can take place before treatment in the simulator or CT simulator, and/or during treatment using portal imaging. Quality assurance (QA) is essential and it is of paramount importance for each member of the planning team to be familiar with the overall process. Patient position and immobilisation For radiotherapy to be effective it must be delivered accurately, and it is important to understand the methods of immobilisation and the inevitable uncertainties in the delivery of treatment.

Introduction: Volatile organic compounds (VOC9s) present in exhaled breath reflect the metabolic activity of the body and change in the presence of both respiratory disease and lung cancer. Human breath analysis is a non-invasive technique for the rapid identification of gas-phase analytes, such as VOC9s, and offers a new clinical diagnostic tool. Ion Mobility Spectrometry coupled with a Multi Capillary Column (MCC/IMS) allows exhaled breath to be rapidly analysed and characterised with great precision. Aim: To derive a database of exhaled breath profiles from participants with and without respiratory disease and to use this database to determine if breath borne VOC9s can be used to differentiate disease states. Methodology: Breath samples from 323 respiratory patients with and without lung cancer were measured using the MCC/IMS and analysed in real time (mean age 68 years, 195 males and 128 females). Demographic data, medical diagnosis and medical history were also collected. Results: The respiratory data were compared to control data from 182 healthy participants of the general public and NHS staff. All breath profiles collected were analysed using advanced chemometric techniques developed in collaboration with Radboud University, Nijmegen, Netherlands. This analysis determined which exhaled breath VOC9s have the potential to differentiate disease. Conclusion: The study has shown that lung cancer can be identified with 87% specificity and 70% sensitivity from healthy controls, reiterating the potential of breath analysis as a diagnosis tool.

Background The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004–2007. Methods Routinely collected population-based data were obtained on all adults (15–99 years) diagnosed with lung cancer in 2004–2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. Results Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. Conclusions There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.

TPS5604Background: Ovarian cancer is the second most common gynaecological malignancy in the Western world. The majority of patients present in an advanced stage and the survival rates are still po...

Objective We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival. Methods Data from population-based cancer registries in Australia, Canada, Denmark, Norway, and the UK were analysed for 20,073 women diagnosed with ovarian cancer during 2004–07. We compare the stage distribution between countries and estimate stage-specific one-year net survival and the excess hazard up to 18months after diagnosis, using flexible parametric models on the log cumulative excess hazard scale. Results One-year survival was 69% in the UK, 72% in Denmark and 74–75% elsewhere. In Denmark, 74% of patients were diagnosed with FIGO stages III–IV disease, compared to 60–70% elsewhere. International differences in survival were evident at each stage of disease; women in the UK had lower survival than in the other four countries for patients with FIGO stages III–IV disease (61.4% vs. 65.8–74.4%). International differences were widest for older women and for those with advanced stage or with no stage data. Conclusion Differences in stage at diagnosis partly explain international variation in ovarian cancer survival, and a more adverse stage distribution contributes to comparatively low survival in Denmark. This could arise because of differences in tumour biology, staging procedures or diagnostic delay. Differences in survival also exist within each stage, as illustrated by lower survival for advanced disease in the UK, suggesting unequal access to optimal treatment. Population-based data on cancer survival by stage are vital for cancer surveillance, and global consensus is needed to make stage data in cancer registries more consistent.