Exploring constructions of female surgeons' intersecting identities and their impacts: a qualitative interview study with clinicians and patients in Ireland and Scotland.

Introduction: While many studies have explored surgeons' personal and professional identities separately, our study is the first to examine intersecting female surgical identities. We explore intersecting surgical identities constructed by self and others (colleagues and patients) within two healthcare systems and their perceived impacts answering the research question: How do female surgeons' constructed identities intersect, and what influences do those intersections have on their surgical lives? Methods: We employed qualitative methodology drawing on semi-structured biographical narrative interviews underpinned by social constructionism. We employed intersectionality theory as an analytical lens. We adopted maximum variation sampling to identify diverse participants, including 38 surgeons (29 female; 9 male), 9 non-surgical colleagues (8 female, 1 male), and 13 patients of female surgeons (7 female, 6 male). Our 29 female surgeons also included six who had transitioned out of surgery. We analyzed the dataset using a five-step Framework Analysis approach. We captured talk about identities, as well as identity talk (constructions of identity through participants' talk). Findings: Multiple intersecting personal (not just gender) and professional identities were constructed and reported to have multiple impacts on female surgeons' lives (including their education, training, and success). We present intersecting identities and their impacts relating to gender through four primary intersections: (a) gender + ethnic identities; (b) gender + parenthood identities; (c) gender + age identities; and (d) gender + professional identities (namely carer, competent, mentor/mentee, role model and leader). Our findings particularly highlight the challenges experienced by female surgeons of color, who are mothers, who are younger and/or who are leaders, illustrating diversity in women's experiences beyond that of gender alone. Finally, we found unexpected insights into male surgeons and fatherhood. Discussion: Intersectionality theory offered a novel analytical lens to extend existing knowledge on female surgical identities. Further research is warranted exploring intersecting identities of female surgeons of color, younger female surgeons, and male surgeons who are fathers, as well as identities unexplored in this study (e.g., diverse sexualities). We need to raise awareness of intersecting identities and their impacts in surgery, as well as providing training, allyship, and policy revision that is sensitive to intersectionality.

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial.

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy. Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival. Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024. Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery. Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy. Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13). Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups. Trial Registration: isrctn.org Identifier: ISRCTN59757862.

Shifting the narrative and practice of assessing professionalism in dietetics education: An Australasian qualitative study.

AIM: We aimed to explore current approaches to assessing professionalism in dietetics education in Australia and New Zealand, and asked the questions what is working well and what needs to improve? METHOD: We employed a qualitative interpretive approach and conducted interviews with academic and practitioner (workplace-based) educators (total sample n = 78) with a key stake in dietetics education across Australia and New Zealand. Data were analysed using team-based, framework analysis. RESULTS: Our findings suggest significant shifts in dietetics education in the area of professionalism assessment. Professionalism assessment is embedded in formal curricula of dietetics programs and is occurring in university and placement settings. In particular, advances have been demonstrated in those programs assessing professionalism as part of the programmatic assessment. Progress has been enabled by philosophical and curricula shifts; clearer articulation and shared understandings of professionalism standards; enhanced learner agency and reduced power distance; early identification and intervention of professionalism lapses; and increased confidence and capabilities of educators. CONCLUSIONS: These findings suggest there have been considerable advances in professionalism assessment in recent years with shifts in practice in approaching professionalism through a more interpretivist lens, holistically and more student-centred. Professionalism assessment in dietetics education is a shared responsibility and requires further development and transformation to more fully embed and strengthen curricula approaches across programs. Further work should investigate strategies to build safer learning cultures and capacity for professionalism conversations and in strengthening approaches to remediation.

SCOT: Tumor Sidedness and the Influence of Adjuvant Chemotherapy Duration on Disease Free Survival (DFS).

AIM: Patients with loco-regional right-sided colorectal tumors have a worse overall survival (OS). Here we investigate the difference in disease free survival (DFS) between colorectal patients with right and left sided tumors in the SCOT study. METHODS: The SCOT study showed 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) is non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. We divided the cohort into patients with left and right sided tumors, and evaluated the effect on DFS and the principle 3 versus 6-months analysis. RESULTS: 6088 patients with Stage III/high risk Stage II colorectal cancers were randomized between 27th March 2008 and 29th November 2013 from 244 centers internationally. In February 2017 (3-years FU) information on sidedness was available for 3309 patients (1238 R-sided, 2071 L-sided). Patients with right-sided tumors had a significantly worse DFS (3-year DFS right: 73.3% (se = 1.3%), left: 80.2% (se = 0.9%) HR 1.423 (95% CI 1.237-1.637; P < .0001). Adjusting for T and N-stage reduced the HR to 1.230 (95% CI 1.066-1.420, P = .005). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR 1.024 [0.831-1.261], L: HR 0.944 [0.783-1.139]). Test for heterogeneity, P = .571. Further sub-set analysis was limited due to cohort size. CONCLUSIONS: This is the first study to show that unselected patients with right-sided tumors had a worse DFS compared to left-sided tumors. Tumor sidedness did not impact upon the 3-months versus 6-months comparison in SCOT.

Gender Matters: Understanding Transitions in Surgical Education.

Introduction: Diverse transitions are elemental to medical career trajectories. The effective navigation of such transitions influences a sense of belonging and wellbeing, positive relationships, and good engagement and attainment within new contexts. Using Multiple and Multidimensional Transitions (MMT) theory as an analytical lens, this paper aims to answer the research question: "What gendered transitions do female surgeons experience, and how do these gendered transitions impact them?" Methods: We conducted a qualitative study drawing on narrative inquiry, with face-to-face and online semi-structured interviews with 29 female surgeons across nine surgical specialities in Ireland and Scotland. This paper is part of a larger study including male surgeons, other colleagues and patients of female surgeons. The female surgeons in this paper were purposively sampled using maximum variation sampling across several levels (consultants, trainees and middle-grade doctors), as well as six who had transitioned out of surgery. Framework analysis was employed to interrogate the interview data. Results: Five overarching types of transitions were identified across surgical education but only three of these transitions-work, culture and health-were primarily experienced by female surgeons (not male surgeons so were considered gendered), thereby impacting social, academic, and psychological domains. The remaining two types of transition-education and geography-were seemingly experienced equally by female and male surgeons, so are beyond the scope of this paper focused on female surgeons' gendered experiences. Conclusion: This novel qualitative study drawing on MMT theory illustrates how multiple gendered transitions interact and impact female surgeons across the surgical education continuum. Aligned with MMT theory, family members and others are also purportedly affected by female surgeons' transitions. Healthcare educators, leaders and policymakers need to better understand gendered transitions and their impacts to improve support for female surgical trainees on their educational journeys.

"We Are Our Own Worst Enemies": A Qualitative Exploration of Sociocultural Factors in Dietetic Education Influencing Student-Dietitian Transitions.

BACKGROUND: The transition from student to dietitian is an implicit expectation of dietetic education. Although there has been an expanding literature around elements of competency-based education, little attention has focused on sociocultural aspects of learning and professional identity formation in dietetic education. OBJECTIVE: The aim of this study was to explore sociocultural factors in dietetics education influencing the transition into the profession from the perspective of dietetics students and educators. DESIGN: An exploratory qualitative study underpinned by social constructionism. PARTICIPANTS/SETTING: From March 2018 until June 2019, interviews (individual and group) with final-year students (n = 22), dietetic preceptors (n = 27), and university faculty members (n = 51) from 17 of the 18 universities in Australia and New Zealand with accredited dietetic programs were undertaken and explored sociocultural factors in dietetic education. ANALYSIS PERFORMED: Data were analyzed into key themes using framework analysis and applying the sociocultural theory of landscapes of practice. RESULTS: Sociocultural factors are powerful influences on the student-professional transition. Dietetic cultures and minicultures of cohesion, conformity, competition, and conflict aversion exist. Boundaries exist within learning environments, which can limit or pose challenges to professional identity formation and transition into the profession. CONCLUSION: Stakeholders involved in dietetics education play pivotal roles in shaping the microcultures students learn and work within, which influence and impact socialization and transition into the profession. Opportunities exist to re-vision curriculum and foster positive learning cultures with a focus on sociocultural learning, including supporting boundary crossing and professional identity development.

Outcomes and survival following neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus: Inverse propensity score weighted analysis.

BACKGROUND: Esophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach. METHODS: Demographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate. RESULTS: Data for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p = 0.807), including major complications (24.0% vs. 23.6%, p = 0.943) and anastomotic leak (7.8% vs. 5.6%, p = 0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p = 0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p = 0.006. There was no difference between groups for overall or disease-free survival. CONCLUSION: This study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are still lacking.

3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT.

BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894).

Patients diagnosed with bowel cancer are likely to have surgery to remove the tumour. Patients diagnosed with a more advanced stage of the disease are then likely to be offered what is known as adjuvant chemotherapy ­ chemotherapy to kill any cancer cells that have already spread but cannot be seen. Adjuvant chemotherapy is usually given over 6 months using two medicines known as oxaliplatin and fluoropyrimidine. This chemotherapy has side effects of diarrhoea, nausea and vomiting, and it reduces the numbers of cells in the blood. It can also damage nerves, which causes discomfort, numbness and tingling; in some cases, this can go on for years. These side effects are more likely to develop with longer treatment. This study looked at whether or not shortening the time over which patients were given oxaliplatin and fluoropyrimidine chemotherapy reduced its effectiveness. In this large study of over 6000 patients, half of the patients were allocated by chance to be treated for 3 months and the other half to be treated for 6 months. Reducing the time that patients had chemotherapy from 6 months to 3 months did not make the treatment less effective. When patients treated with chemotherapy over 3 months were compared with those treated over 6 months, 77% of patients in both groups were well with no detectable disease 3 years after surgery. Patients were less likely to get side effects with 3-month chemotherapy. In particular, the chance of persistent long-term nerve damage was lower, resulting in patients with 3-month chemotherapy having better health-related quality of life. Overall, the study showed that 3-month adjuvant chemotherapy for patients with bowel cancer is as effective as 6-month adjuvant chemotherapy and causes fewer side effects.

Healthcare professionals' perceptions of learning communication in the healthcare workplace: an Australian interview study.

OBJECTIVES: The literature focuses on teaching communication skills in the 'classroom', with less focus on how such skills are informally learnt in the healthcare workplace. We grouped healthcare work based on the cure:care continuum to explore communication approaches based on work activities. This study asks: 1) How do healthcare professionals believe they learn communication in the workplace? 2) What are the differences (if any) across the 'type of work' as represented by the cure:care continuum? DESIGN: This qualitative study used semi-structured individual interviews. SETTING: Community care and acute hospitals in Australia (Victoria and New South Wales). PARTICIPANTS: Twenty qualified healthcare professionals (medicine n=4, nursing n=3, allied health n=13) from various clinical specialties (eg, acute, rehabilitation, surgery, palliative care) participated. METHODS: Data were analysed using framework analysis, which involved the development of a thematic coding framework. Findings were mapped to participants' descriptions of work using the cure:care continuum. RESULTS: Three themes were identified that varied across the cure:care continuum: professional discourse-tying communication approaches to work activities; personal identities-the influence of personal identities on healthcare communication and role modelling-the influence of others in the socially bound context of healthcare work. CONCLUSIONS: This study highlights the influence of professional, personal and social factors on the learning of healthcare communication in the workplace. Our study illuminates differences in communication practice related to work activities, as conceptualised by the cure:care continuum. The results call for further examination of the 'nature' of work activities and the concomitant influence on developing healthcare communication.

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial.

BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes. METHODS: Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC). RESULTS: Samples were available from n = 117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P < 0.001 and P = 0.02, respectively). CONCLUSIONS: Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation.

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Women in medical education: views and experiences from the Kingdom of Saudi Arabia.

CONTEXT: Although research from Western contexts suggests that considerable inequalities for female medical educators exist in the workplace, we do not yet know the views and experiences of women within non-Western contexts. By examining the influence of context, intersecting identities and language use, this study explores female medical educators' views and experiences of gender, career progression and leadership in academic medicine in the Kingdom of Saudi Arabia (KSA). METHODS: We conducted individual interviews employing narrative interviewing techniques with 25 female medical educators from five schools in the KSA (June to December 2014). Data were analysed using framework analysis and drew on intersectionality theory. RESULTS: Participants expressed their views and experiences of career progression, leadership and gendered workplace cultures. Women's experiences of career progression and leadership in the KSA were influenced by their gender and varied according to their career stage, work environment and specialty. Participants discussed the gendered organisational cultures of academic medicine in the KSA in terms of gender inequalities (e.g. females being overlooked for leadership positions), gender stereotypes (e.g. women perceived as more likely to take part in shared leadership) and gendered specialties (e.g. surgery being male dominated). We revealed women's more tacit understandings about gender, career progression and leadership by examining how they talk (e.g. metaphoric, pronominal and emotional talk). Finally, participants constructed multiple intersecting personal (e.g. female, mother and young) and professional identities (e.g. doctor, teacher and leader) for themselves through their narratives. CONCLUSION: This study provides important new insights into female medical educators' experiences of career progression and leadership in a non-Western context. Investment in the future of women's careers in the KSA through faculty development initiatives and equality and diversity policies is now essential to help close the gender gap.

Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.

BACKGROUND: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. METHODS: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012. RESULTS: The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. CONCLUSIONS: Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial.

BACKGROUND: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival. METHODS: In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK. Patients were eligible if they had an ECOG performance status of 0-1 and an estimated life expectancy of longer than 3 months. Patients were given first-line cisplatin and gemcitabine chemotherapy (25 mg/m(2) cisplatin and 1000 mg/m(2) gemcitabine [on days 1 and 8 every 21 days, for up to eight cycles]) with either 20 mg oral cediranib or placebo once a day until disease progression. We randomly assigned patients (1:1) with a minimisation algorithm, incorporating the stratification factors: extent of disease, primary disease site, previous treatment, ECOG performance status, and centre. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00939848, and was closed on Sept 30, 2014; results of the final analysis for the primary endpoint are presented. FINDINGS: Between April 5, 2011, and Sept 28, 2012, we enrolled 124 patients (62 in each group). With a median follow-up of 12·2 months (IQR 7·3-18·5), median progression-free survival was 8·0 months (95% CI 6·5-9·3) in the cediranib group and 7·4 months (5·7-8·5) in the placebo group (HR 0·93, 80% CI 0·74-1·19, 95% CI 0·65-1·35; p=0·72). Patients who received cediranib had more grade 3-4 toxic effects than did patients who received placebo: hypertension (23 [37%] vs 13 [21%]; p=0·05), diarrhoea (eight [13%] vs two [3%]; p=0·05); platelet count decreased (ten [16%] vs four [6%]; p=0·09), white blood cell decreased (15 [24%] vs seven [11%]; p=0·06) and fatigue (16 [24%] vs seven [11%]; p=0·04). INTERPRETATION: Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine, which remains the standard of care. Although patients in the cediranib group had more adverse events, we recorded no unexpected toxic effects. The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational. FUNDING: Cancer Research UK and AstraZeneca Pharmaceuticals.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus.

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS.

The information-seeking behaviours of partners of men with prostate cancer: a qualitative pilot study.

This pilot study explores in depth the information-seeking behaviours of partners of men with prostate cancer. Six men with prostate cancer and their partners participated in one mini focus group discussion or four couple interviews. Theme analysis by two independent analysts produced three related themes: partners' information-seeking behaviours; partners' information-avoiding behaviours; and the conflict between seeking and avoiding information. The information-seeking behaviours of partners were individualistic, with some partners seeking voluminous information and others avoiding information. Partners sought information to help reduce their feelings of anxiety and uncertainty, to help them participate in the decision-making process, to help them care for their partner and to ensure that they had their information needs met. Partners avoided information to reduce their levels of fear and worry and to maintain a sense of normality. They failed to seek information from healthcare professionals because they felt disempowered and pressurised for time during patient-physician consultations. The information-seeking behaviours of partners changed over time and across situations and their behaviours were sometimes different from those of their partners (the patients), with some partners exhibiting more information-seeking behaviour than patients. The findings within each of these themes and their practice implications are discussed in this paper.

Development of a reliable and valid questionnaire to test the prostate cancer knowledge of men with the disease.

Several prostate cancer knowledge questionnaires exist but none have demonstrated both reliability and validity when used by men with the disease. This study aims to develop a reliable and valid knowledge questionnaire for men with prostate cancer. After developing a 40-item Prostate Cancer Knowledge Questionnaire (PCKQ-40) in phase I, it was piloted in phase II with 391 medical students. This resulted in the reduction of the tool by removing items of poor discriminatory value. A balance between true and false items and content domains was also maintained in the reduced scale. The PCKQ-12 had a moderate internal consistency. Phase III of the study assessed the reliability and construct validity of the tool by measuring the prostate cancer knowledge levels of men with prostate cancer (n=28), men with other cancers (n=10) and men without cancer (n=84). Men with prostate cancer achieved significantly higher PCKQ-12 scores compared with men without cancer, supporting the construct validity of the tool. The tool's reliability was also confirmed with a moderate internal consistency. This study provides some evidence for the reliability and validity of the PCKQ-12 and supports its use with men with prostate cancer in further research.

Phase I trial of ZD9331, a nonpolyglutamatable thymidylate synthase inhibitor, given as a 5-day continuous infusion to patients with refractory solid malignancies.

PURPOSE: This dose-escalating study investigated the toxicity, pharmacokinetics, and efficacy of the novel direct-acting antifolate ZD9331, given as a 5-day i.v. infusion every 3 weeks. EXPERIMENTAL DESIGN: Forty-five patients with refractory solid malignancies received ZD9331, which was escalated from 0.125 mg/m(2)/day. RESULTS: Dose-limiting grade 4 thrombocytopenia occurred in 3 of 6 patients treated at 8 mg/m(2)/day; other drug-related toxicities, across dose levels, included skin and gastrointestinal toxicity, lethargy, and asymptomatic, reversible, elevated transaminases. The maximum plasma concentration and area under the curve increased with dose. Clearance was dose-dependent and predominantly renal. At doses >/=2.4 mg/m(2)/day, plasma 2'-deoxyuridine levels were elevated consistently indicating inhibition of thymidylate synthase. Two patients had a partial response (breast, 1 patient; ovarian, 1 patient), and 10 patients had stable disease. CONCLUSION: The maximum tolerated dose was defined as 6 mg/m(2)/day, and the toxicity profile for this regimen was considered acceptable and manageable. Administration of ZD9331 lead to elevation of 2'-deoxyuridine levels, signifying thymidylate synthase inhibition, and evidence of antitumor activity was observed.

Evaluating the reliability and validity of three tools to assess the quality of health information on the Internet.

The quality of Internet information needs to be evaluated and several tools exist for this purpose. However, none have demonstrated reliability and validity. This study tested the internal consistency and validity of the information quality tool (IQT), quality scale (QS) and DISCERN using 89 web sites discussing smoking cessation. The inter-rater reliability of the tools was established by exploring the agreement between two independent raters for 22 (25%) of the sites. The IQT and DISCERN possessed satisfactory internal consistency (as measured by Cronbach's alpha). The IQT, QS and DISCERN showed satisfactory inter-rater reliability (as measured by kappa and intraclass correlations). The IQT, QS and DISCERN correlated positively with each other, supporting the convergent validity of the tools. This study provides some evidence for the reliability and validity of the IQT, QS and DISCERN, although this needs testing in further research with different types of Internet information and larger sample sizes.