This is the ICR’s publications repository, an open access repository of full-text research articles and theses by ICR staff and students.

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    Intensity standardization of MRI prior to radiomic feature extraction for artificial intelligence research in glioma-a systematic review.
    (SPRINGER, 2022-10-01) Fatania, K; Mohamud, F; Clark, A; Nix, M; Short, SC; O'Connor, J; Scarsbrook, AF; Currie, S; O'Connor, James Patrick
    OBJECTIVES: Radiomics is a promising avenue in non-invasive characterisation of diffuse glioma. Clinical translation is hampered by lack of reproducibility across centres and difficulty in standardising image intensity in MRI datasets. The study aim was to perform a systematic review of different methods of MRI intensity standardisation prior to radiomic feature extraction. METHODS: MEDLINE, EMBASE, and SCOPUS were searched for articles meeting the following eligibility criteria: MRI radiomic studies where one method of intensity normalisation was compared with another or no normalisation, and original research concerning patients diagnosed with diffuse gliomas. Using PRISMA criteria, data were extracted from short-listed studies including number of patients, MRI sequences, validation status, radiomics software, method of segmentation, and intensity standardisation. QUADAS-2 was used for quality appraisal. RESULTS: After duplicate removal, 741 results were returned from database and reference searches and, from these, 12 papers were eligible. Due to a lack of common pre-processing and different analyses, a narrative synthesis was sought. Three different intensity standardisation techniques have been studied: histogram matching (5/12), limiting or rescaling signal intensity (8/12), and deep learning (1/12)-only two papers compared different methods. From these studies, histogram matching produced the more reliable features compared to other methods of altering MRI signal intensity. CONCLUSION: Multiple methods of intensity standardisation have been described in the literature without clear consensus. Further research that directly compares different methods of intensity standardisation on glioma MRI datasets is required. KEY POINTS: • Intensity standardisation is a key pre-processing step in the development of robust radiomic signatures to evaluate diffuse glioma. • A minority of studies compared the impact of two or more methods. • Further research is required to directly compare multiple methods of MRI intensity standardisation on glioma datasets.
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    Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature.
    (SPRINGER, 2022-03-01) Waqar, M; Trifiletti, DM; McBain, C; O'Connor, J; Coope, DJ; Akkari, L; Quinones-Hinojosa, A; Borst, GR; O'Connor, James Patrick
    PURPOSE OF REVIEW: Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy though unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review, we discuss the clinical implications and biological foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically. RECENT FINDINGS: Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise and compare these strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss the most promising strategies that could benefit future glioblastoma patients. There is biological rationale to suggest that early interventions could improve the outcome of glioblastoma patients and they should be investigated in future trials.
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    Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.
    (ELSEVIER, 2022-04-01) Zhou, C; O'Connor, J; Backen, A; Valle, JW; Bridgewater, J; Dive, C; Jayson, GC; O'Connor, James Patrick
    BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment. PATIENTS AND METHODS: Patients (n = 124) with advanced biliary tract cancer (ABC) received cisplatin/gemcitabine with cediranib or placebo (ABC-03 trial). Concentrations of pTie2 were measured longitudinally from before treatment until disease progression. Data from patients with ovarian cancer (n = 92, ICON7 trial) and patients with colorectal cancer (CRC) (n = 70, Travastin trial) were also included. RESULTS: Cediranib-treated ABC patients were deconvoluted into distinct groups where in one group pTie2 trajectories resembled those seen in placebo-treated patients and in another pTie2 significantly reduced (t-test P = 2.7 × 10-14). Using the 95% confidence interval for these two groups, we defined a vascular complete response (vCR) as a 24% reduction in pTie2 within 9 weeks; vascular no response (vNR) as a 7% increase in pTie2, and a vascular partial response (between these limits). vCR cediranib-treated patients had significantly improved progression-free survival (8.8 versus 7.5 months, restricted mean ratio 0.73, P = 0.012) and overall survival (18.8 versus 12.1 months, hazard ratio 0.49, P = 0.02). By integrating data across ovarian cancer, CRC and ABC, we show that (i) patients with vNR do not benefit from VEGFi and (ii) Tie2-defined vascular progression occurs sufficiently in advance of radiological progressive disease that changes in treatment could be offered to prevent clinical deterioration. CONCLUSION: pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.
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    Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.
    (WILEY, 2024-03-01) Kim, M; Naish, JH; Needleman, SH; Tibiletti, M; Taylor, Y; O'Connor, JPB; Parker, GJM; O'Connor, James Patrick
    PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.
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    Surgical Management of Primary Anorectal Melanoma: Is Less More?
    (SPRINGER, 2024-06-01) Fadel, MG; Mohamed, HS; Weir, J; Hayes, AJ; Larkin, J; Smith, MJ; Mohamed, Hesham Mohamed Sayed; Larkin, James; Smith, Myles
    PURPOSE: Ano-uro-genital (AUG) Mucosal Melanoma UK guidelines recommended a less radical surgical strategy for anorectal melanoma (ARM) where possible. We report our experience of ARM consistent with that approach including clinical presentation, intervention undertaken and prognosis. METHODS: We present a retrospective study of 15 consecutive patients with ARM surgically treated between November 2014 and April 2023. Patients were divided into the two surgery types: wide local excision (WLE, n = 9) and abdominoperineal resection (APR, n = 6). Data on demographics, diagnosis, treatment and oncological outcomes were assessed between the groups. RESULTS: The mean age was 65.3 ± 17.4 years and 6 (40.0%) were female patients. Nine patients (60.0%) were diagnosed with stage I and six patients (40.0%) with stage II disease. R0 margins were achieved in all cases. The overall mean length of stay was lower following WLE compared to APR (2.6 ± 2.4 days versus 14.0 ± 9.8 days, p = 0.032). Two complications were observed in the WLE group compared to four complications after APR (p = 0.605). Five patients (55.5%) developed local/distant recurrence in the WLE group compared to three patients (50.0%) in the APR group (p = 0.707), with a median overall survival of 38.5 (12-83) months versus 26.5 (14-48) months, respectively. CONCLUSIONS: Achieving clear margins by the least radical fashion may have equivalent oncological outcomes to radical surgery, potentially reducing patient morbidity and preserving function. In our experience, the surgical management of ARM consistent with the 'less is more' approach adhering to AUG guidelines has acceptable outcomes.

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