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  Exploring the use of Rasch modelling in “common content” items for multi-site and multi-year assessment

  Hope, D; Kluth, D; Homer, M; Dewar, A; Goddard-Fuller, Rikki; Jaap, A; Cameron, H; Christie Education, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK. (Springer Science and Business Media LLC, 2024-07-08)

  Rasch modelling is a powerful tool for evaluating item performance, measuring drift in difficulty over time, and comparing students who sat assessments at different times or at different sites. Here, we use data from thirty UK medical schools to describe the benefits of Rasch modelling in quality assurance and the barriers to using it. Sixty "common content" multiple choice items were offered to all UK medical schools in 2016-17, and a further sixty in 2017-18, with five available in both years. Thirty medical schools participated, for sixty total datasets across two sessions, and 14,342 individual sittings. Schools selected items to embed in written assessment near the end of their programmes. We applied Rasch modelling to evaluate unidimensionality, model fit statistics and item quality, horizontal equating to compare performance across schools, and vertical equating to compare item performance across time. Of the sixty sittings, three provided non-unidimensional data, and eight violated goodness of fit measures. Item-level statistics identified potential improvements in item construction and provided quality assurance. Horizontal equating demonstrated large differences in scores across schools, while vertical equating showed item characteristics were stable across sessions. Rasch modelling provides significant advantages in model- and item- level reporting compared to classical approaches. However, the complexity of the analysis and the smaller number of educators familiar with Rasch must be addressed locally for a programme to benefit. Furthermore, due to the comparative novelty of Rasch modelling, there is greater ambiguity on how to proceed when a Rasch model identifies misfitting or problematic data.
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  Comparing survival of perihilar cholangiocarcinoma after R1 resection versus palliative chemotherapy for unresected localized disease

  van Keulen, A. M.; Buettner, S.; Olthof, P. B.; Klümpen, H. J.; Erdmann, J. I.; Izquierdo-Sanchez, L.; Banales, J. M.; Goeppert, B.; Roessler, S.; Zieniewicz, K.; et al. (2024)

  BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.
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  VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint

  Wanstall, Hannah C; Korysko, P.; Farabolini, W.; Corsini, R.; Bateman, J. J.; Rieker, V.; Hemming, Abigail; Henthorn, Nicholas T; Merchant, Michael J; Santina, Elham; et al. (2024)

  Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 10(9) Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.
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  Validation of the BOADICEA model in a prospective cohort of <i>BRCA1/2</i> pathogenic variant carriers

  Yang, X.; Mooij, T. M.; Leslie, G.; Ficorella, L.; Andrieu, N.; Kast, K.; Singer, C. F.; Jakubowska, A.; van Gils, C. H.; Tan, Y. Y.; et al. (2024)

  Background No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres. Methods We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information. Results The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options. Conclusion BOADICEA may be used to aid personalised cancer risk management and decision-making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).
• Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy

  Toussaint, L.; Matysiak, W.; Alapetite, C.; Aristu, J.; Bannink-Gawryszuk, A.; Bolle, S.; Bolsi, A.; Calvo, F.; Cerron Campoo, F.; Charlwood, Frances; et al. (2024)

  BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

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