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  Inter-school variations in the standard of examiners' graduation-level OSCE judgements

  Yeates, P.; Maluf, A.; McCray, G.; Kinston, R.; Cope, N.; Cullen, K.; O'Neill, V.; Cole, A.; Chung, C. W.; Goodfellow, R.; et al. (2024)

  IntroductionEnsuring equivalence in high-stakes performance exams is important for patient safety and candidate fairness. We compared inter-school examiner differences within a shared OSCE and resulting impact on students' pass/fail categorisation.MethodsThe same 6 station formative OSCE ran asynchronously in 4 medical schools, with 2 parallel circuits/school. We compared examiners' judgements using Video-based Examiner Score Comparison and Adjustment (VESCA): examiners scored station-specific comparator videos in addition to 'live' student performances, enabling 1/controlled score comparisons by a/examiner-cohorts and b/schools and 2/data linkage to adjust for the influence of examiner-cohorts. We calculated score impact and change in pass/fail categorisation by school.ResultsOn controlled video-based comparisons, inter-school variations in examiners' scoring (16.3%) were nearly double within-school variations (8.8%). Students' scores received a median adjustment of 5.26% (IQR 2.87-7.17%). The impact of adjusting for examiner differences on students' pass/fail categorisation varied by school, with adjustment reducing failure rate from 39.13% to 8.70% (school 2) whilst increasing failure from 0.00% to 21.74% (school 4).DiscussionWhilst the formative context may partly account for differences, these findings query whether variations may exist between medical schools in examiners' judgements. This may benefit from systematic appraisal to safeguard equivalence. VESCA provided a viable method for comparisons.
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  A randomised phase II trial of hippocampal sparing versus conventional whole brain radiotherapy after surgical resection or radiosurgery in favourable prognosis patients with 1-10 brain metastases

  Whitfield, Gillian A; Bulbeck, H.; Clifton-Hadley, L.; Edwards, D.; Jefferies, S.; Jenkinson, M. D.; Griffin, M.; Handley, Julia; Megias, D.; Sanghera, P.; et al. (2024)

  AIMS: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. MATERIALS AND METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. CONCLUSION: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.
• Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer

  Vergote, I.; González-Martin, A.; Fujiwara, K.; Kalbacher, E.; Bagaméri, A.; Ghamande, S.; Lee, J. Y.; Banerjee, S.; Maluf, F. C.; Lorusso, D.; et al. (2024)

  Background Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy. Methods We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. Results A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects. Conclusions In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.)
• Research progress on sexual functioning and associated factors in childhood cancer survivors: a scoping review

  Yang, F. N.; Ho, K. Y.; Yorke, Janelle; Lam, K. K. W.; Liu, Q.; Guo, L. W.; Fai, N. G. C.; Liu, P. Y. A.; Yuen, J.; Belay, G. M.; et al. (2024)

  Background Childhood Cancer Survivors (CCSs) are more likely to report sexual dysfunction than people without cancer history. Sexual functioning encompasses more than just sexual dysfunction. The scarcity of information regarding the status and in fl uencing factors of sexual functioning in CCSs, hampers to devise suitable screening or interventions. This review aims to summarize research progress on sexual functioning and associated factors among CCSs. Methods This review protocol is registered in PROSPERO(CRD42023427939) and performed according to PRISMA guidelines. From inception to November 15, 2023, a comprehensive search was conducted in PubMed, EMBASE, CINAHL, Web of Science, SCOPUS, PsycINFO, CNKI Database, Wanfang of Chinese Database, SinoMed Database and Cochrane Library on sexual functioning and childhood cancer survivors. Inclusion criteria were English or Chinese studies focusing on sexual functioning and related factors of cancer survivors, who diagnosed with cancer before 18 years old, and were adult and disease-free when participating in the study. Studies were excluded if the focus was on adult cancer patients or without age information. Findings 395 records were retrieved, and 22 studies were fi nally included in this review. Results suggest that CCSs experience a substantial burden of sexual issues, including delayed psychosexual development, low satisfaction, and high prevalence of dysfunction. Underlying factors related to sexual functioning of CCSs were identi fi ed, including demographic, cancer treatment-related, psychological, and physiological factors. The historical change in research on sexual functioning was summarized. Interpretation Research on sexual functioning among CCSs is limited. The extent to which cancer and related treatments affect sexual functioning remains largely unknown. The relationships between various factors and mechanisms underlying sexual functioning need to be con fi rmed by more rigorous studies to enable effective interventions to be developed. Funding None. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• Turning the tide in aggressive lymphoma: liquid biopsy for risk-adapted treatment strategies

  Wang, S.; Mouliere, Florent; Pegtel, D. M.; Chamuleau, M. E. D.; Cancer Research UK National Biomarker Centre, University of Manchester, Wilmslow Road, Manchester, UK (2024)

  Diffuse large B cell lymphoma (DLBCL) exhibits significant biological and clinical heterogeneity that presents challenges for risk stratification and disease surveillance. Existing tools for risk stratification, including the international prognostic index (IPI), tissue molecular analyses, and imaging, have limited accuracy in predicting outcomes. The therapeutic landscape for aggressive lymphoma is rapidly evolving, and there is a pressing need to identify patients at risk of refractory or relapsed (R/R) disease in the context of personalized therapy. Liquid biopsy, a minimally invasive method for cancer signal detection, has been explored to address these challenges. We review advances in liquid biopsy strategies focusing on circulating nucleic acids in DLBCL patients and highlight their clinical potential. We also provide recommendations for biomarkerguided trials to support risk-adapted treatment modalities.

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