Imperial College London

ProfessorEricAboagye

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 3313 3759eric.aboagye

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

GN1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

469 results found

Boubnovski Martell M, Linton-Reid K, Chen M, Hindocha S, Moreno P, Alvarez-Benito M, Salvatierra A, Lee R, Posma J, Calzado M, Aboagye Eet al., 2024, Deep representation learning of tissue metabolome and computed tomography annotates NSCLC classification and prognosis, npj Precision Oncology, Vol: 8, ISSN: 2397-768X

The rich chemical information from tissue metabolomics provides a powerful means to elaborate tissue physiology or tumor characteristics at cellular and tumor microenvironment levels. However, the process of obtaining such information requires invasive biopsies, is costly, and can delay clinical patient management. Conversely, computed tomography (CT) is a clinical standard of care but does not intuitively harbor histological or prognostic information. Furthermore, the ability to embed metabolome information into CT to subsequently use the learned representation for classification or prognosis has yet to be described. This study develops a deep learning-based framework -- tissue-metabolomic-radiomic-CT (TMR-CT) by combining 48 paired CT images and tumor/normal tissue metabolite intensities to generate ten image embeddings to infer metabolite-derived representation from CT alone. In clinical NSCLC settings, we ascertain whether TMR-CT results in an enhanced feature generation model solving histology classification/prognosis tasks in an unseen international CT dataset of 742 patients. TMR-CT non-invasively determines histological classes - adenocarcinoma/squamous cell carcinoma with an F1-score = 0.78 and further asserts patients’ prognosis with a c-index = 0.72, surpassing the performance of radiomics models and deep learning on single modality CT feature extraction. Additionally, our work shows the potential to generate informative biology-inspired CT-led features to explore connections between hard-to-obtain tissue metabolic profiles and routine lesion-derived image data.

Journal article

Ma Q, Wang X, Feng B, Liang C, Wan X, El-Newehy M, Abdulhameed MM, Mo X, Wu Jet al., 2024, Fiber configuration determines foreign body response of electrospun scaffolds:in vitroandin vivoassessments., Biomed Mater, Vol: 19

Biomaterial scaffolds boost tissue repair and regeneration by providing physical support, delivering biological signals and/or cells, and recruiting endogenous cells to facilitate tissue-material integration and remodeling. Foreign body response (FBR), an innate immune response that occurs immediately after biomaterial implantation, is a critical factor in determining the biological outcomes of biomaterial scaffolds. Electrospinning is of great simplicity and cost-effectiveness to produce nanofiber scaffolds with well-defined physicochemical properties and has been used in a variety of regenerative medicine applications in preclinical trials and clinical practice. A deep understanding of causal factors between material properties and FBR of host tissues is beneficial to the optimal design of electrospun scaffolds with favorable immunomodulatory properties. We herein prepared and characterized three electrospun scaffolds with distinct fiber configurations and investigated their effects on FBR in terms of immune cell-material interactions and host responses. Our results show that electrospun yarn scaffold results in greater cellular immune reactions and elevated FBR inin vivoassessments. Although the yarn scaffold showed aligned fiber bundles, it failed to induce cell elongation of macrophages due to its rough surface and porous grooves between yarns. In contrast, the aligned scaffold showed reduced FBR compared to the yarn scaffold, indicating a smooth surface is also a contributor to the immunomodulatory effects of the aligned scaffold. Our study suggests that balanced porousness and smooth surface of aligned fibers or yarns should be the key design parameters of electrospun scaffolds to modulate host responsein vivo.

Journal article

Aboagye E, Dubash S, Barwick TD, Kozlowski K, Rockall AG, Khan S, Khan S, Yusuf S, Lamarca A, Valle JW, Hubner RA, Mcnamara MG, Tan T, Wernig F, Todd J, Meeran K, Pratap B, Azeem S, Huiban M, Keat N, Lozano-Kuehne J, Sharma Ret al., 2023, Somatostatin receptor imaging with [18F]-FET-βAG-TOCA PET/CT and [68Ga]Ga-DOTA peptide PET/CT in patients with neuroendocrine neoplasms: A prospective, phase II comparative study, The Journal of Nuclear Medicine

Journal article

Rajgor AD, Kui C, McQueen A, Cowley J, Gillespie C, Mill A, Rushton S, Obara B, Bigirumurame T, Kallas K, O'Hara J, Aboagye E, Hamilton DWet al., 2023, CT-based radiomic markers are independent prognosticators of survival in advanced laryngeal cancer: A pilot study., J Laryngol Otol, Pages: 1-25

Journal article

Challapalli A, Barwick TD, Dubash SR, Inglese M, Grech-Sollars M, Kozlowski K, Tam H, Patel NH, Winkler M, Flohr P, Saleem A, Bahl A, Falconer A, De Bono JS, Aboagye EO, Mangar Set al., 2023, Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH)., Molecules, Vol: 28

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Journal article

Rockall AG, Li X, Johnson N, Lavdas I, Santhakumaran S, Prevost AT, Punwani S, Goh V, Barwick TD, Bharwani N, Sandhu A, Sidhu H, Plumb A, Burn J, Fagan A, Wengert GJ, Koh D-M, Reczko K, Dou Q, Warwick J, Liu X, Messiou C, Tunariu N, Boavida P, Soneji N, Johnston EW, Kelly-Morland C, De Paepe KN, Sokhi H, Wallitt K, Lakhani A, Russell J, Salib M, Vinnicombe S, Haq A, Aboagye EO, Taylor S, Glocker Bet al., 2023, Development and evaluation of machine learning in whole-body magnetic resonance imaging for detecting metastases in patients with lung or colon cancer: a diagnostic test accuracy study, Investigative Radiology, Vol: 58, Pages: 823-831, ISSN: 0020-9996

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient spec

Journal article

Hunter B, Argyros C, Inglese M, Linton-Reid K, Pulzato I, Nicholson AG, Kemp SV, L Shah P, Molyneaux PL, Mcnamara C, Burn T, Guilhem E, Mestas Nunez M, Hine J, Choraria A, Ratnakumar P, Bloch S, Jordan S, Padley S, Ridge CA, Robinson G, Robbie H, Barnett J, Silva M, Desai S, Lee RW, Aboagye EO, Devaraj Aet al., 2023, Radiomics-based decision support tool assists radiologists in small lung nodule classification and improves lung cancer early diagnosis, BRITISH JOURNAL OF CANCER, ISSN: 0007-0920

Journal article

Aboagye E, Islam S, Inglese M, Grech-Sollars M, Aravind P, Dubash S, Barwick TD, ONeill K, Saleem A, O'Callaghan J, Anchini G, Williams M, Waldman Aet al., 2023, Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 50, Pages: 3982-3995, ISSN: 0340-6997

Purpose:MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study.Methods:Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade – LGG – and higher-grade – HGG – patients). FPIA was injected as an intravenous bolus injection (range 342–368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min.Results:All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG.Conclusion:Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population.

Journal article

Piletsky S, Baidyuk E, Piletska EV, Lezina L, Shevchenko K, Jones DJL, Cao TH, Singh R, Spivey A, Aboagye E, Piletsky S, Barlev Net al., 2023, Modulation of EGFR activity by molecularly imprinted polymer nanoparticles targeting intracellular epitopes, Nano Letters: a journal dedicated to nanoscience and nanotechnology, Vol: 23, Pages: 9677-9682, ISSN: 1530-6984

In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.

Journal article

Murphy R, Chander G, Martinez M, Ward C, Khan SR, Naik M, Barwick TD, Aboagye EO, Sharma Ret al., 2023, Study protocol of LANTana: A phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours, United Kingdom, BMJ Open, Vol: 13, ISSN: 2044-6055

Introduction: Suitability for peptide receptor radionuclide therapy (PRRT) for neuroendocrine neoplasia (NENs) depends on presence of somatostatin receptor-2 (SSTR2) determined by [68Ga]Ga-DOTA-peptide-positron emission tomography (PET). Some patients have low or no uptake on [68Ga]Ga-DOTA-peptide-PET, precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. Demethylating agents increase uptake on PET imaging in vivo such that tumours previously negative on PET become positive, correlating with a dose dependent increase in tumoural SSTR2 expression. LANTana will determine whether treatment with the demethylating agent, ASTX727, results in re-expression of SSTR2 using [68Ga]Ga-DOTA-peptide-PET to image epigenetic modification of the SSTR2 locus, allowing subsequent PRRT.Methods and analysis: 27 participants with a histologic diagnosis of NEN (Ki67<55%) with no or low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT will be recruited. Patients will receive 5 days of ASTX727 (fixed dose 35mg decitabine + 100mg cedazuridine). [68Ga]Ga-DOTA-peptide-PET/CT will be repeated day 8+2; where there is significant uptake greater than liver in most lesions, PRRT will be administered. Primary objective is to determine re-expression of SSTR2 on PET imaging. Tolerability, progression free survival, overall response and quality of life will be assessed. Methylation in peripheral blood mononuclear cells and tumoral methylation will be evaluated. Ethics and dissemination: LANTana has ethical approval from Leeds West Research Ethics Committee (REC Reference: 21/YH/0247).Sponsored by Imperial College London and funded by Advanced Accelerator Applications pharmaceuticals. Results will be presented at conferences and submitted to peer-reviewed journals for publication and will be available on ClinicalTrials.gov.Trial registration numbers: EUDRACT number: 2020-003800-15, NCT05178693

Journal article

Yang Z, Barnes C, Domarkas J, Koch-Paszkowski J, Wright J, Amgheib A, Renard I, Fu R, Archibald S, Aboagye EO, Allott Let al., 2023, Automated sulfur-[<SUP>18</SUP>F]fluoride exchange radiolabelling of a prostate specific membrane antigen (PSMA) targeted ligand using the GE FASTlab™ cassette-based platform, REACTION CHEMISTRY & ENGINEERING, Vol: 8, Pages: 2403-2407, ISSN: 2058-9883

Journal article

Welgemoed C, Spezi E, Riddle P, Gooding MJ, Gujral D, McLauchlan R, Aboagye EOet al., 2023, Clinical evaluation of atlas-based auto-segmentation in breast and nodal radiotherapy., Br J Radiol, Vol: 96

OBJECTIVES: Accurate contouring of anatomical structures allows for high-precision radiotherapy planning, targeting the dose at treatment volumes and avoiding organs at risk. Manual contouring is time-consuming with significant user variability, whereas auto-segmentation (AS) has proven efficiency benefits but requires editing before treatment planning. This study investigated whether atlas-based AS (ABAS) accuracy improves with template atlas group size and character-specific atlas and test case selection. METHODS AND MATERIALS: One clinician retrospectively contoured the breast, nodes, lung, heart, and brachial plexus on 100 CT scans, adhering to peer-reviewed guidelines. Atlases were clustered in group sizes, treatment positions, chest wall separations, and ASs created with Mirada software. The similarity of ASs compared to reference contours was described by the Jaccard similarity coefficient (JSC) and centroid distance variance (CDV). RESULTS: Across group sizes, for all structures combined, the mean JSC was 0.6 (SD 0.3, p = .999). Across atlas-specific groups, 0.6 (SD 0.3, p = 1.000). The correlation between JSC and structure volume was weak in both scenarios (adjusted R2-0.007 and 0.185).Mean CDV was similar across groups but varied up to 1.2 cm for specific structures. CONCLUSIONS: Character-specific atlas groups and test case selection did not improve accuracy outcomes. High-quality ASs were obtained from groups containing as few as ten atlases, subsequently simplifying the application of ABAS. CDV measures indicating auto-segmentation variations on the x, y, and z axes can be utilised to decide on the clinical relevance of variations and reduce AS editing. ADVANCES IN KNOWLEDGE: High-quality ABASs can be obtained from as few as ten template atlases.Atlas and test case selection do not improve AS accuracy.Unlike well-known quantitative similarity indices, volume displacement metrics provide information on the location of segmentation variations, helping ass

Journal article

Chen M, Copley SJ, Viola P, Lu H, Aboagye EOet al., 2023, Radiomics and artificial intelligence for precision medicine in lung cancer treatment, SEMINARS IN CANCER BIOLOGY, Vol: 93, Pages: 97-113, ISSN: 1044-579X

Journal article

Aboagye E, Aravind P, Popat S, Barwick TD, Soneji N, Lythgoe M, Sreter KB, Lozano- Kuehne JP, Bergqvist M, Patel N, Kenny LMet al., 2023, A subset of non-small cell lung cancer patients treated with pemetrexed show 18f-fluorothymidine ‘flare’ on positron emission tomography, Cancers, Vol: 15, Pages: 1-14, ISSN: 2072-6694

Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the

Journal article

Aboagye E, Lu H, Lou H, Wengert G, Paudel R, Patel N, Desai S, Crum W, Linton-Reid K, Chen M, Li D, Ip J, Mauri F, Pinato DJ, Rockall A, Copley SJ, Ghaem-Maghami Set al., 2023, Tumour and local lymphoid tissue interaction determines prognosis in high grade serous ovarian cancer, Cell Reports Medicine, Vol: 4, Pages: 1-24, ISSN: 2666-3791

Tertiary lymphoid structure (TLS) is associated with prognosis in copy number-driven tumours,including high grade serous ovarian cancer (HGSOC), although the function of TLS and its interactionwith copy-number alterations in HGSOC is not fully understood. In the current study, we confirmthat TLS-high HGSOC patients show significantly better progression free survival. We show thatpresence of TLS in HGSOC tumours is associated with B-cell maturation and cytotoxic tumourspecific T-cells activation and proliferation. Additionally, the copy number loss of IL15 and CXCL10may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed.Manuscript Click here to view linked ReferencesLastly, a radiomics-based signature is developed to predict presence of TLS, which independentlypredicts PFS in both HGSOC patients and ICI-treated NSCLC patients. Overall, we reveal that TLScoordinates intratumoural B-cell and T-cell response against HGSOC tumour, while cancer genomeevolves to counteract TLS formation and function.

Journal article

Aboagye E, Teh JH, Amgheib A, Fu R, Barnes C, Abrahams J, Ashek A, Wang N, Yang Z, Mansoorudeen M, Long NJ, Aboagye Eet al., 2023, Evaluation of [18F]AlF-EMP-105 for molecular imaging of 2 C-Met, Pharmaceutics, Vol: 15, Pages: 1-13, ISSN: 1999-4923

C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer.

Journal article

Talbot T, Lu H, Aboagye EO, 2023, Amplified therapeutic targets in high-grade serous ovarian carcinoma - a review of the literature with quantitative appraisal, CANCER GENE THERAPY, Vol: 30, Pages: 955-963, ISSN: 0929-1903

Journal article

Kalantar R, Hindocha S, Hunter B, Sharma B, Khan N, Koh D-M, Ahmed M, Aboagye EOO, Lee RWW, Blackledge MDDet al., 2023, Non-contrast CT synthesis using patch-based cycle-consistent generative adversarial network (Cycle-GAN) for radiomics and deep learning in the era of COVID-19, SCIENTIFIC REPORTS, Vol: 13, ISSN: 2045-2322

Journal article

Sharma R, Ward C, Naik M, Khan S, Barwick T, Martinez M, Izadi H, Aboagye EOet al., 2023, LANTana trial protocol: An open label, single arm, phase Ib study to evaluate the effect of pre-treatment with ASTX727 (a demethylating agent) followed by lutetium Lu 177 dotatate in patients with progressive, metastatic neuroendocrine neoplasias (NENs)., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X

Conference paper

Li X, Marcus D, Russell J, Aboagye E, Ellis L, Sheeka A, Park W-HE, Bharwani N, Ghaem-Maghami S, Rockall Aet al., 2023, An integrated clinical-MR radiomics model to estimate survival time in patients with endometrial cancer, Journal of Magnetic Resonance Imaging, Vol: 57, Pages: 1922-1933, ISSN: 1053-1807

Background:Determination of survival time in women with endometrial cancer using clinical features remains imprecise. Features from MRI may improve the survival estimation allowing improved treatment planning.Purpose:To identify clinical features and imaging signatures on T2-weighted MRI that can be used in an integrated model to estimate survival time for endometrial cancer subjects.Study Type:Retrospective.Population:Four hundred thirteen patients with endometrial cancer as training (N = 330, 66.41 ± 11.42 years) and validation (N = 83, 67.60 ± 11.89 years) data and an independent set of 82 subjects as testing data (63.26 ± 12.38 years).Field Strength/Sequence:1.5-T and 3-T scanners with sagittal T2-weighted spin echo sequence.Assessment:Tumor regions were manually segmented on T2-weighted images. Features were extracted from segmented masks, and clinical variables including age, cancer histologic grade and risk score were included in a Cox proportional hazards (CPH) model. A group least absolute shrinkage and selection operator method was implemented to determine the model from the training and validation datasets.Statistical Tests:A likelihood-ratio test and decision curve analysis were applied to compare the models. Concordance index (CI) and area under the receiver operating characteristic curves (AUCs) were calculated to assess the model.Results:Three radiomic features (two image intensity and volume features) and two clinical variables (age and cancer grade) were selected as predictors in the integrated model. The CI was 0.797 for the clinical model (includes clinical variables only) and 0.818 for the integrated model using training and validation datasets, the associated mean AUC value was 0.805 and 0.853. Using the testing dataset, the CI was 0.792 and 0.882, significantly different and the mean AUC was 0.624 and 0.727 for the clinical model and integrated model, respective

Journal article

Chen M, Lu H, Copley SJ, Han Y, Logan A, Viola P, Cortellini A, Pinato DJ, Power D, Aboagye EOet al., 2023, A novel radiogenomics biomarker for predicting treatment response and pneumotoxicity from programmed cell death protein or ligand-1 inhibition immunotherapy in NSCLC, Journal of Thoracic Oncology, Vol: 18, Pages: 718-730, ISSN: 1556-0864

INTRODUCTION: Patient selection for checkpoint inhibitor immunotherapy is currently guided by programmed death-ligand 1 (PD-L1) expression obtained from immunohistochemical staining of tumor tissue samples. This approach is susceptible to limitations resulting from the dynamic and heterogeneous nature of cancer cells and the invasiveness of the tissue sampling procedure. To address these challenges, we developed a novel computed tomography (CT) radiomic-based signature for predicting disease response in patients with NSCLC undergoing programmed cell death protein 1 (PD-1) or PD-L1 checkpoint inhibitor immunotherapy. METHODS: This retrospective study comprises a total of 194 patients with suitable CT scans out of 340. Using the radiomic features computed from segmented tumors on a discovery set of 85 contrast-enhanced chest CTs of patients diagnosed with having NSCLC and their CD274 count, RNA expression of the protein-encoding gene for PD-L1, as the response vector, we developed a composite radiomic signature, lung cancer immunotherapy-radiomics prediction vector (LCI-RPV). This was validated in two independent testing cohorts of 66 and 43 patients with NSCLC treated with PD-1 or PD-L1 inhibition immunotherapy, respectively. RESULTS: LCI-RPV predicted PD-L1 positivity in both NSCLC testing cohorts (area under the curve [AUC] = 0.70, 95% confidence interval [CI]: 0.57-0.84 and AUC = 0.70, 95% CI: 0.46-0.94). In one cohort, it also demonstrated good prediction of cases with high PD-L1 expression exceeding key treatment thresholds (>50%: AUC = 0.72, 95% CI: 0.59-0.85 and >90%: AUC = 0.66, 95% CI: 0.45-0.88), the tumor's objective response to treatment at 3 months (AUC = 0.68, 95% CI: 0.52-0.85), and pneumonitis occurrence (AUC = 0.64, 95% CI: 0.48-0.80). LCI-RPV achieved statistically significant stratification of the patients into a high- and low-risk survival group (hazard ratio = 2.26, 95% CI: 1.21-4.24, p = 0.011 a

Journal article

Aboagye EO, Barwick TD, Haberkorn U, 2023, Radiotheranostics in oncology: Making precision medicine possible, CA-A CANCER JOURNAL FOR CLINICIANS, Vol: 73, Pages: 255-274, ISSN: 0007-9235

Journal article

Li X, Aboagye E, Michele D, Diana M, James R, Laura Burney E, Alexander S, Won-Ho Edward P, Nishat B, Sadaf G-M, Rockall Aet al., 2023, Prediction of deep myometrial infiltration, clinical risk category, histological type, and lymphovascular space invasion in women with endometrial cancer based on clinical and T2-weighted MRI radiomic features, Cancers, Vol: 15, ISSN: 2072-6694

Deep myometrial infiltration, clinical risk score, histological type, and lymphovascular space invasion are important clinical variables that have significant management implications for endometrial cancer patients. Determination of these factors using pure T2-weighted MRI is time-consuming, and the accuracy of this relies on the experience of the clinicians. Combining clinical information and radiomic features from MRI, we developed machine learning classification models to predict these clinical variables. Based on a training dataset, an automatic selection classification model with an optimized hyperparameters method was adopted to find the optimal classifiers. The accuracy of the model predictions was evaluated using an independent external testing dataset. The results suggest that an integrated model (combining clinical and radiomic features) achieved a reasonable accuracy for endometrial cancer clinical variable prediction. The application of these models in clinical practice could potentially lead to cost reductions and personalized treatment.

Journal article

Lu H, Wengert G, Lou H, Paudel R, Patel N, Desai S, Crum B, Linton-Reid K, Chen M, Li D, Ip J, Mauri F, Pinato DJ, Rockall A, Copley SJ, Ghaem-Maghami S, Aboagye EOet al., 2023, Tumour and local lymphoid tissue interaction determines prognosis in high grade serous ovarian cancer, 114th Annual Meeting of the American Association for Cancer Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JMet al., 2023, Somatostatin receptor PET/MR imaging of inflammation in patients with large vessel vasculitis and atherosclerosis., Journal of the American College of Cardiology, Vol: 81, Pages: 336-354, ISSN: 0735-1097

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macropha

Journal article

Hunter B, Chen M, Ratnakumar P, Alemu E, Logan A, Linton-Reid K, Tong D, Senthivel N, Bhamani A, Bloch S, Kemp S, Boddy L, Jain S, Gareeboo S, Rawal B, Doran S, Navani N, Nair A, Bunce C, Kaye S, Blackledge M, Aboagye E, Devaraj A, Lee Ret al., 2022, A radiomics-based decision support tool improves lung cancer diagnosis in combination with the Herder score in large lung nodules, EBioMedicine, Vol: 86, ISSN: 2352-3964

Background:Large lung nodules (≥15 mm) have the highest risk of malignancy, and may exhibit important differences in phenotypic or clinical characteristics to their smaller counterparts. Existing risk models do not stratify large nodules well. We aimed to develop and validate an integrated segmentation and classification pipeline, incorporating deep-learning and traditional radiomics, to classify large lung nodules according to cancer risk.Methods:502 patients from five U.K. centres were recruited to the large-nodule arm of the retrospective LIBRA study between July 2020 and April 2022. 838 CT scans were used for model development, split into training and test sets (70% and 30% respectively). An nnUNet model was trained to automate lung nodule segmentation. A radiomics signature was developed to classify nodules according to malignancy risk. Performance of the radiomics model, termed the large-nodule radiomics predictive vector (LN-RPV), was compared to three radiologists and the Brock and Herder scores.Findings:499 patients had technically evaluable scans (mean age 69 ± 11, 257 men, 242 women). In the test set of 252 scans, the nnUNet achieved a DICE score of 0.86, and the LN-RPV achieved an AUC of 0.83 (95% CI 0.77–0.88) for malignancy classification. Performance was higher than the median radiologist (AUC 0.75 [95% CI 0.70–0.81], DeLong p = 0.03). LN-RPV was robust to auto-segmentation (ICC 0.94). For baseline solid nodules in the test set (117 patients), LN-RPV had an AUC of 0.87 (95% CI 0.80–0.93) compared to 0.67 (95% CI 0.55–0.76, DeLong p = 0.002) for the Brock score and 0.83 (95% CI 0.75–0.90, DeLong p = 0.4) for the Herder score. In the international external test set (n = 151), LN-RPV maintained an AUC of 0.75 (95% CI 0.63–0.85). 18 out of 22 (82%) malignant nodules in the Herder 10–70% category in the test set were identified as high risk by the decision-support tool, and may have been referred for earl

Journal article

Hindocha S, Charlton TG, Linton-Reid K, Hunter B, Chan C, Ahmed M, Greenlay EJ, Orton M, Bunce C, Lunn J, Doran SJ, Ahmad S, McDonald F, Locke I, Power D, Blackledge M, Lee RW, Aboagye EOet al., 2022, Author Correction: Gross tumour volume radiomics for prognostication of recurrence & death following radical radiotherapy for NSCLC, NPJ PRECISION ONCOLOGY, Vol: 6

Journal article

Evans JS, Beaumont J, Braga M, Masrour N, Mauri F, Beckley A, Butt S, Karali CS, Cawthorne C, Archibald S, Aboagye EO, Sharma Ret al., 2022, Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy, European Journal of Cancer, Vol: 176, Pages: 110-120, ISSN: 0959-8049

BackgroundSomatostatin receptor-2 (SSTR2) is expressed on cell surface of neuroendocrine neoplasias; its presence is exploited for the delivery of peptide receptor radionuclide therapy (PRRT). Patients with no or low expression of SSTR2 are not candidates for PRRT. SSTR2 promotor undergoes epigenetic modification, known to regulate gene expression. We investigated whether the demethylation agent, guadecitabine, could enhance the expression of SSTR2 in NET models, using radioligand uptake/PET imaging as a biomarker of epigenetic modification.MethodsThe effects of guadecitabine on the transcriptional, translational, and functional regulation of SSTR2 both in vitro and in vivo using low (QGP-1) and high (BON-1) methylated neuroendocrine neoplasia models was characterised. Promotor region methylation profiling of clinical samples (n = 61) was undertaken. Safety of combination guadecitabine and PRRT was assessed in vivo.ResultsPyrosequencing of cell lines illustrated differential methylation indices – BON: 1 94%, QGP: 1 21%. Following guadecitabine treatment, a dose-dependent increase in SSTR2 in BON-1 at a transcriptional, translational, and functional levels using the SSTR2-directed radioligand, 18F-FET-βAG-TOCA ([18F]-FETO) (150% increase [18F]-FETO uptake, p < 0.05) was observed. In vivo, guadecitabine treatment resulted in a 70% increase in [18F]-FETO uptake in BON-1 tumour models compared models with low baseline percentage methylation (p < 0.05). No additive toxicity was observed with the combination treatment of PRRT and guadecitabine in vivo. Methylation index in clinical samples was 10.5% compared to 5.2% in controls (p = 0.03) and correlated with SSTR2 expression (Wilcoxon rank sign −3.75,p < 0.01).ConclusionGuadecitabine increases SSTR2 expression both in vitro and in vivo. The combination of demethylation agents with PRRT warrants further investigation.

Journal article

Islam S, Inglese M, Aravind P, Barwick T, Wang J, O'Neill K, Waldman A, Williams M, Aboagye EOet al., 2022, 18F-Fluoropivalate PET/MRI: imaging of treatment naive patients and patients treated with radiosurgery, 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: Elsevier, Pages: S49-S49, ISSN: 0959-8049

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