Imperial College London

DrMatthewWilliams

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 3311 0733matthew.williams Website CV

 
 
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Location

 

Charing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
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94 results found

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, ISSN: 0340-6997

Journal article

Dadhania S, Pakzad-Shahabi L, Mistry S, Williams Met al., 2023, Triaxial accelerometer-measured physical activity and functional behaviours among people with High Grade Glioma: The BrainWear Study, PLoS One, Vol: 18, Pages: 1-21, ISSN: 1932-6203

BACKGROUND: High-grade gliomas (HGG) account for 60-75% of all adult gliomas. The complexity of treatment, recovery and survivorship creates a need for novel monitoring approaches. Accurate assessment of physical function plays a vital role in clinical evaluation. Digital wearable tools could help us address unmet needs by offering unique advantages such as scale, cost and continuous real-world objective data. We present data from 42 patients enrolled into the BrainWear study. METHODS: An AX3 accelerometer was worn by patients from diagnosis or at recurrence. Age-, sex-matched UK Biobank control groups were chosen for comparison. RESULTS: 80% of data were categorised as high-quality demonstrating acceptability. Remote, passive monitoring identifies moderate activity reduces both during a course of radiotherapy (69 to 16 minutes/day) and at the time of progressive disease assessed by MRI (72 to 52 minutes/day). Mean acceleration (mg) and time spent walking daily (h/day) correlated positively with the global health quality of life and physical functioning scores and inversely with the fatigue score. Healthy controls walked on average 2.91h/day compared to 1.32h/day for the HGG group on weekdays and 0.91h/day on the weekend. The HGG cohort slept for longer on weekends (11.6h/day) than weekdays (11.2h/day) compared to healthy controls (8.9h/day). CONCLUSION: Wrist-worn accelerometers are acceptable and longitudinal studies feasible. HGG patients receiving a course of radiotherapy reduce their moderate activity by 4-fold and are at least half as active as healthy controls at baseline. Remote monitoring can provide a more informed and objective understanding of patient activity levels to help optimise health related quality of life (HRQoL) among a patient cohort with an extremely limited lifespan.

Journal article

Tallant J, Pakzad-Shahabi L, Lambert SD, Williams M, Wells Met al., 2023, Quality of Life in Caregivers of Patients with Brain Tumours: A Systematic Review and Thematic Analysis, European Journal of Cancer Care, Vol: 2023, Pages: 1-12

<jats:p>Objective. (1) Examine QoL of caregivers of patients with brain tumours compared to population norms and other cancer caregiver groups, (2) appraise the content of quantitative QoL outcome measures utilised, and (3) assess to what extent QoL measures used in research align with caregivers’ priorities. Methods. Systematic literature search of studies including caregivers of brain tumour patients using self-completed assessments of QoL. Extracted data from included studies included quantitative QoL outcome data, QoL outcome measures utilised, and the included QoL domains. The impact of brain tumour patient caregiving was assessed by summarising included data comparing brain tumour caregivers to other cancer caregivers and normative population data. QoL measures utilised by the studies and their domains were extracted, coded, and analysed by themes. The rates of investigation by theme were then compared to existing data on caregiver-own preference in relation to QoL. Results. 49 studies, including 57 outcome measures, incorporating a combined 124 QoL domains. Brain tumour caregivers reported lower QoL outcomes than population norms but similar to other cancer caregiver groups. Thematic analysis of QoL domains generated 7 themes: caregiving burden and adaptation, existential and self, family and social support, finances, information needs, physical symptoms and functioning, and psychological symptoms and wellbeing. The most investigated themes were physical and psychological symptoms, the most important for caregivers themselves were family and social support. Conclusions. Caregiving for brain tumour patients is shown to negatively affect QoL, particularly mental health, burden, and social life. Existing QoL research in caregivers of brain tumour patients predominantly utilises generic QoL measures designed for use in patients and draws a medicalised view of QoL priorities. The few studies using caregiver-specific QoL measures demonstrated closer ali

Journal article

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S2 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;Kaplan Meier plots for PFS and OS&lt;/p&gt;</jats:p>

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Data from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;div&gt;AbstractPurpose:&lt;p&gt;Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (&lt;i&gt;ASS1&lt;/i&gt;) and/or argininosuccinate lyase (&lt;i&gt;ASL&lt;/i&gt;). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed.&lt;/p&gt;Patients and Methods:&lt;p&gt;We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16–06/17) to receive weekly ADI-PEG20 36 mg/m&lt;sup&gt;2&lt;/sup&gt; intramuscularly plus pemetrexed 500 mg/m&lt;sup&gt;2&lt;/sup&gt; and cisplatin 75 mg/m&lt;sup&gt;2&lt;/sup&gt; intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy.&lt;/p&gt;Results:&lt;p&gt;Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti–ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5–20.8) and overall survival was 6.3 months (95%

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S3 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;Effects of ADI-PEG20 on the folate pathway&lt;/p&gt;</jats:p>

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S2 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;Kaplan Meier plots for PFS and OS&lt;/p&gt;</jats:p>

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S1 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;ASS1 immunohistochemistry&lt;/p&gt;</jats:p>

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Data from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;div&gt;AbstractPurpose:&lt;p&gt;Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (&lt;i&gt;ASS1&lt;/i&gt;) and/or argininosuccinate lyase (&lt;i&gt;ASL&lt;/i&gt;). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed.&lt;/p&gt;Patients and Methods:&lt;p&gt;We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16–06/17) to receive weekly ADI-PEG20 36 mg/m&lt;sup&gt;2&lt;/sup&gt; intramuscularly plus pemetrexed 500 mg/m&lt;sup&gt;2&lt;/sup&gt; and cisplatin 75 mg/m&lt;sup&gt;2&lt;/sup&gt; intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy.&lt;/p&gt;Results:&lt;p&gt;Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti–ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5–20.8) and overall survival was 6.3 months (95%

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S1 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;ASS1 immunohistochemistry&lt;/p&gt;</jats:p>

Other

Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu B-W, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PWet al., 2023, Figure S3 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

<jats:p>&lt;p&gt;Effects of ADI-PEG20 on the folate pathway&lt;/p&gt;</jats:p>

Other

Dadhania S, Williams M, 2023, What is so Special About Digital Health in Cancer?, Clin Oncol (R Coll Radiol), Vol: 35, Pages: 147-149

Journal article

Pati S, Baid U, Edwards B, Sheller M, Wang S-H, Reina GA, Foley P, Gruzdev A, Karkada D, Davatzikos C, Sako C, Ghodasara S, Bilello M, Mohan S, Vollmuth P, Brugnara G, Preetha CJ, Sahm F, Maier-Hein K, Zenk M, Bendszus M, Wick W, Calabrese E, Rudie J, Villanueva-Meyer J, Cha S, Ingalhalikar M, Jadhav M, Pandey U, Saini J, Garrett J, Larson M, Jeraj R, Currie S, Frood R, Fatania K, Huang RY, Chang K, Balaña C, Capellades J, Puig J, Trenkler J, Pichler J, Necker G, Haunschmidt A, Meckel S, Shukla G, Liem S, Alexander GS, Lombardo J, Palmer JD, Flanders AE, Dicker AP, Sair HI, Jones CK, Venkataraman A, Jiang M, So TY, Chen C, Heng PA, Dou Q, Kozubek M, Lux F, Michálek J, Matula P, Keřkovský M, Kopřivová T, Dostál M, Vybíhal V, Vogelbaum MA, Mitchell JR, Farinhas J, Maldjian JA, Yogananda CGB, Pinho MC, Reddy D, Holcomb J, Wagner BC, Ellingson BM, Cloughesy TF, Raymond C, Oughourlian T, Hagiwara A, Wang C, To M-S, Bhardwaj S, Chong C, Agzarian M, Falcão AX, Martins SB, Teixeira BCA, Sprenger F, Menotti D, Lucio DR, LaMontagne P, Marcus D, Wiestler B, Kofler F, Ezhov I, Metz M, Jain R, Lee M, Lui YW, McKinley R, Slotboom J, Radojewski P, Meier R, Wiest R, Murcia D, Fu E, Haas R, Thompson J, Ormond DR, Badve C, Sloan AE, Vadmal V, Waite K, Colen RR, Pei L, Ak M, Srinivasan A, Bapuraj JR, Rao A, Wang N, Yoshiaki O, Moritani T, Turk S, Lee J, Prabhudesai S, Morón F, Mandel J, Kamnitsas K, Glocker B, Dixon LVM, Williams M, Zampakis P, Panagiotopoulos V, Tsiganos P, Alexiou S, Haliassos I, Zacharaki EI, Moustakas K, Kalogeropoulou C, Kardamakis DM, Choi YS, Lee S-K, Chang JH, Ahn SS, Luo B, Poisson L, Wen N, Tiwari P, Verma R, Bareja R, Yadav I, Chen J, Kumar N, Smits M, van der Voort SR, Alafandi A, Incekara F, Wijnenga MMJ, Kapsas G, Gahrmann R, Schouten JW, Dubbink HJ, Vincent AJPE, van den Bent MJ, French PJ, Klein S, Yuan Y, Sharma S, Tseng T-C, Adabi S, Niclou SP, Keunen O, Hau A-C, Vallières M, Fortin D, Lepage M, Landman B, Ramadass K, Xu K, Chotai S, Chambless LB, Miet al., 2023, Author Correction: Federated learning enables big data for rare cancer boundary detection., Nature Communications, Vol: 14, Pages: 436-436, ISSN: 2041-1723

Journal article

Muirhead R, Dean C, Diez P, Williams M, McDonald Fet al., 2023, Launch of the UK SABR Consortium Pelvic Stereotactic Ablative Radiotherapy Re-irradiation Guidelines and National Audit, CLINICAL ONCOLOGY, Vol: 35, Pages: 29-32, ISSN: 0936-6555

Journal article

Dumba M, Fry A, Shelton J, Booth TC, Jones B, Shuaib H, Williams Met al., 2022, Imaging in patients with glioblastoma: A national cohort study, Neuro-Oncology Practice, Vol: 9, Pages: 487-495, ISSN: 2054-2585

BackgroundGlioblastoma is the most common malignant brain tumor in adults and has a poor prognosis. This cohort of patients is diverse and imaging is vital to formulate treatment plans. Despite this, there is relatively little data on patterns of use of imaging and imaging workload in routine practice.MethodsWe examined imaging patterns for all patients aged 15–99 years resident in England who were diagnosed with a glioblastoma between 1st January 2013 and 31st December 2014. Patients without imaging and death-certificate-only registrations were excluded.ResultsThe analytical cohort contained 4,307 patients. There was no significant variation in pre- or postdiagnostic imaging practice by sex or deprivation quintile. Postdiagnostic imaging practice was varied. In the group of patients who were treated most aggressively (surgical debulking and chemoradiation) and were MRI compatible, only 51% had a postoperative MRI within 72 hours of surgery. In patients undergoing surgery who subsequently received radiotherapy, only 61% had a postsurgery and preradiotherapy MRI.ConclusionsPrediagnostic imaging practice is uniform. Postdiagnostic imaging practice was variable. With increasing evidence and clearer recommendations regarding debulking surgery and planning radiotherapy imaging, the reason for this is unclear and will form the basis of further work.

Journal article

Zhang K, Toni F, Williams M, 2022, A federated cox model with non-proportional hazards, The 6th International Workshop on ​Health Intelligence, Publisher: Springer, Pages: 171-185, ISSN: 1860-949X

Recent research has shown the potential for neural networksto improve upon classical survival models such as the Cox model, whichis widely used in clinical practice. Neural networks, however, typicallyrely on data that are centrally available, whereas healthcare data arefrequently held in secure silos. We present a federated Cox model thataccommodates this data setting and also relaxes the proportional hazardsassumption, allowing time-varying covariate effects. In this latter respect,our model does not require explicit specification of the time-varying ef-fects, reducing upfront organisational costs compared to previous works.We experiment with publicly available clinical datasets and demonstratethat the federated model is able to perform as well as a standard model.

Conference paper

Plaha P, Camp S, Cook J, McCulloch P, Voets N, Ma R, Taphoorn MJB, Dirven L, Grech-Sollars M, Watts C, Bulbeck H, Jenkinson MD, Williams M, Lim A, Dixon L, Price SJ, Ashkan K, Apostolopoulos V, Barber VS, Taylor A, FUTURE-GB collaborators, Nandi Det al., 2022, FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial., BMJ Open, Vol: 12, Pages: 1-10, ISSN: 2044-6055

INTRODUCTION: Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS). METHODS AND ANALYSIS: This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death. ETHICS AND DISSEMINATION: The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN38834571.

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

Conference paper

Rozati H, Williams M, 2022, SURVIVAL OUTCOMES OF STEREOTACTIC RADIOTHERAPY FOR TEN OR MORE BRAIN METASTASES, Publisher: OXFORD UNIV PRESS INC, Pages: 9-9, ISSN: 1522-8517

Conference paper

Kanso N, Le Calvez K, Mauricaite R, Williams Met al., 2022, THE COST OF INPATIENT CARE FOR ADULT PRIMARY BRAIN TUMOUR PATIENTS IN ENGLAND, 17th Meeting of the European-Association-of-Neuro-Oncology, Publisher: OXFORD UNIV PRESS INC, ISSN: 1522-8517

Conference paper

Asavarut P, Waramit S, Suwan K, Marais GJK, Chongchai A, Benjathummarak S, Al-Bahrani M, Vila-Gomez P, Williams M, Kongtawelert P, Yata T, Hajitou Aet al., 2022, Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles, EMBO Molecular Medicine, Vol: 14, Pages: 1-25, ISSN: 1757-4676

Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through transmorphic encapsidation of human recombinant adeno-associated virus DNA using coat proteins from a tumour-targeted bacteriophage (phage). We show that Transmorphic Phage/AAV (TPA) particles provide superior delivery of transgenes over current phage-derived vectors through greater diffusion across the extracellular space and improved intracellular trafficking. We used TPA to target the delivery of cytokine-encoding transgenes for interleukin-12 (IL12), and novel isoforms of IL15 and tumour necrosis factor alpha (TNFα) for tumour immunotherapy. Our results demonstrate selective and efficient gene delivery and immunotherapy against solid tumours in vivo, without harming healthy organs. Our transmorphic particle system provides a promising modality for safe and effective gene delivery, and cancer immunotherapies through cross-species complementation of two commonly used viruses.

Journal article

Chen J, Williams M, Huang Y, Si Set al., 2022, Identifying Topics and Evolutionary Trends of Literature on Brain Metastases Using Latent Dirichlet Allocation, FRONTIERS IN MOLECULAR BIOSCIENCES, Vol: 9

Journal article

Chen J, Sinclair G, Rozati H, Hill L, Pakzad-Shahabi L, Wang J, Calvez KL, Paddick I, Williams Met al., 2022, Improving on whole-brain radiotherapy in patients with large brain metastases: a planning study to support the AROMA clinical trial, Radiotherapy and Oncology, Vol: 170, Pages: 176-183, ISSN: 0167-8140

PURPOSE: To develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. METHODS AND MATERIALS: We identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1cc to the target volumes and organs at risk. RESULTS: Compared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). CONCLUSIONS: VMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs.

Journal article

Pati S, Baid U, Edwards B, Sheller M, Wang S-H, Reina GA, Foley P, Gruzdev A, Karkada D, Davatzikos C, otherset al., 2022, Federated learning enables big data for rare cancer boundary detection, Publisher: arXiv

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Working paper

Hallows R, Glazier L, Katz MS, Aznar M, Williams Met al., 2022, Safe and Ethical Artificial Intelligence in Radiotherapy - Lessons Learned From the Aviation Industry, CLINICAL ONCOLOGY, Vol: 34, Pages: 99-101, ISSN: 0936-6555

Journal article

Mi E, Mauricaite R, Pakzad-Shahabi L, Chen J, Ho A, Williams Met al., 2021, Deep learning-based quantification of temporalis muscle has prognostic value in patients with glioblastoma, British Journal of Cancer, Vol: 126, Pages: 196-203, ISSN: 0007-0920

BackgroundGlioblastoma is the commonest malignant brain tumour. Sarcopenia is associated with worse cancer survival, but manually quantifying muscle on imaging is time-consuming. We present a deep learning-based system for quantification of temporalis muscle, a surrogate for skeletal muscle mass, and assess its prognostic value in glioblastoma.MethodsA neural network for temporalis segmentation was trained with 366 MRI head images from 132 patients from 4 different glioblastoma data sets and used to quantify muscle cross-sectional area (CSA). Association between temporalis CSA and survival was determined in 96 glioblastoma patients from internal and external data sets.ResultsThe model achieved high segmentation accuracy (Dice coefficient 0.893). Median age was 55 and 58 years and 75.6 and 64.7% were males in the in-house and TCGA-GBM data sets, respectively. CSA was an independently significant predictor for survival in both the in-house and TCGA-GBM data sets (HR 0.464, 95% CI 0.218–0.988, p = 0.046; HR 0.466, 95% CI 0.235–0.925, p = 0.029, respectively).ConclusionsTemporalis CSA is a prognostic marker in patients with glioblastoma, rapidly and accurately assessable with deep learning. We are the first to show that a head/neck muscle-derived sarcopenia metric generated using deep learning is associated with oncological outcomes and one of the first to show deep learning-based muscle quantification has prognostic value in cancer.

Journal article

Patel M, Zhan J, Natarajan K, Flintham R, Davies N, Sanghera P, Grist J, Duddalwar V, Peet A, Sawlani Vet al., 2021, Artificial intelligence for early prediction of treatment response in glioblastoma, Neuro-Oncology, Vol: 23, Pages: iv1-iv1, ISSN: 1522-8517

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>Treatment response assessment in glioblastoma is challenging. Patients routinely undergo conventional magnetic resonance imaging (MRI), but it has a low diagnostic accuracy for distinguishing between true progression (tPD) and pseudoprogression (psPD) in the early post-chemoradiotherapy time period due to similar imaging appearances. The aim of this study was to use artificial intelligence (AI) on imaging data, clinical characteristics and molecular information within machine learning models, to distinguish between and predict early tPD from psPD in patients with glioblastoma.</jats:p> </jats:sec> <jats:sec> <jats:title>Method</jats:title> <jats:p>The study involved retrospective analysis of patients with newly-diagnosed glioblastoma over a 3.5 year period (n=340), undergoing surgery and standard chemoradiotherapy treatment, with an increase in contrast-enhancing disease on the baseline MRI study 4-6 weeks post-chemoradiotherapy. Studies had contrast-enhanced T1-weighted imaging (CE-T1WI), T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences, acquired at 1.5 Tesla with 6-months follow-up to determine the reference standard outcome. 76 patients (mean age 55 years, range 18-76 years, 39% female, 46 tPD, 30 psPD) were included. Machine learning models utilised information from clinical characteristics (age, gender, resection extent, performance status), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and 307 quantitative imaging features; extracted from baseline study CE-T1WI/ADC and T2WI sequences using semi-automatically segmented enhancing disease and perilesional oedema masks respectively. Feature selection was performed within bootstrapped cross-validate

Journal article

Sinclair H, Le Calvez K, Chen J, Pakzad-Shahabi L, Dixon L, Mohammed W, Saleem W, Williams Met al., 2021, Estimating population-based incidence of brain metastases–a comprehensive incident cohort study, BNOS 2021 Meeting, Publisher: Oxford University Press, Pages: iv21-iv21, ISSN: 1522-8517

Conference paper

Wang JW, Williams M, 2021, Exploring definitions of radiological sarcopenia in cancer: a protocol for a scoping review, BMJ Open, Vol: 11, ISSN: 2044-6055

Introduction Sarcopenia is the loss of skeletal muscle volume or quality, a concept previously established in age-related frailty. Sarcopenia is part of the cancer cachexia syndrome and has therefore been explored as biomarker through the opportunistic measurement of skeletal muscle from routine cancer imaging. However, there is inconsistency in diagnostic landmarks and cut-offs. The most common assessment method is skeletal muscle area at the slice level of the third lumbar vertebrae divided by height squared. Alternative sarcopenia measures have been derived from morphological descriptions of the psoas, thoracic and cervical muscles, driven by tumour-specific anatomical imaging.Current tumour-site specific reviews suggest a link between heterogeneously defined sarcopenia on tumour site-specific outcomes. Because lack of uniformity, a scoping review is best suited to streamline anatomically based definitions and map the evidence to outcomes. The aim of this article is to describe a protocol for a scoping review that will homogenise the evidence of radiological sarcopenia in cancer. The extent, range and nature of reports will be examined, after which possible titles for potential systematic reviews identified.Methods and analysis We will apply methods based on the Joanna Briggs Institute scoping review manual. Predefined search terms compiled with a librarian experienced in systematic reviews will be used to search PubMed/Medline, Embase, Scopus and Cochrane databases studies correlating cross-sectional cancer sarcopenia biomarkers with clinical outcomes. Studies will be mapped according to whether they have defined new sarcopenia measures or applied previous definitions to new populations, both with reported outcomes. This review will generate a numerical analysis on the extent of cancer sarcopenia measures as well as a narrative synthesis to describe the applications of radiologically derived sarcopenia in cancer.

Journal article

Varughese M, Treece S, Drinkwater K, Williams Met al., 2021, Failing to Close the Gap between Evidence and Clinical Practice in Radical Bladder Cancer Radiotherapy: A Critical Unmet Need, CLINICAL ONCOLOGY, Vol: 33, Pages: 340-341, ISSN: 0936-6555

Journal article

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