Publications
205 results found
Aboagye E, Lu H, Lou H, et 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.
Li X, Marcus D, Russell J, et 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
Kasaven L, Saso S, Barcroft J, et al., 2023, An umbrella review of meta-analyses regarding the incidence of female specific malignancies following fertility treatment, Publisher: OXFORD UNIV PRESS, ISSN: 0268-1161
Li X, Aboagye E, Michele D, et 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.
Lu H, Wengert G, Lou H, et 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
Dannhorn A, Doria ML, McKenzie J, et al., 2023, Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies, METABOLITES, Vol: 13
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Oxley S, Kalra A, Sideris M, et al., 2023, Impact of Multiple COVID-19 Waves on Gynaecological Cancer Services in the UK, CANCERS, Vol: 15
Sundar S, Nordin A, Morrison J, et al., 2023, British Gynaecological Cancer Society Recommendations for Evidence Based, Population Data Derived Quality Performance Indicators for Ovarian Cancer, CANCERS, Vol: 15
Marcus D, Phelps DL, Savage A, et al., 2022, Point-of-care diagnosis of endometrial cancer using the surgical intelligent knife (iknife)-a prospective pilot study of diagnostic accuracy, Cancers, Vol: 14, Pages: 1-14, ISSN: 2072-6694
Introduction: Delays in the diagnosis and treatment of endometrial cancer negatively impact patient survival. The aim of this study was to establish whether rapid evaporative ionisation mass spectrometry using the iKnife can accurately distinguish between normal and malignant endometrial biopsy tissue samples in real time, enabling point-of-care (POC) diagnoses. Methods: Pipelle biopsy samples were obtained from consecutive women needing biopsies for clinical reasons. A Waters G2-XS Xevo Q-Tof mass spectrometer was used in conjunction with a modified handheld diathermy (collectively called the ‘iKnife’). Each tissue sample was processed with diathermy, and the resultant surgical aerosol containing ionic lipid species was then analysed, producing spectra. Principal component analyses and linear discriminant analyses were performed to determine variance in spectral signatures. Leave-one-patient-out cross-validation was used to test the diagnostic accuracy. Results: One hundred and fifty patients provided Pipelle biopsy samples (85 normal, 59 malignant, 4 hyperplasia and 2 insufficient), yielding 453 spectra. The iKnife differentiated between normal and malignant endometrial tissues on the basis of differential phospholipid spectra. Cross-validation revealed a diagnostic accuracy of 89% with sensitivity, specificity, positive predictive value and negative predictive value of 85%, 93%, 94% and 85%, respectively. Conclusions: This study is the first to use the iKnife to identify cancer in endometrial Pipelle biopsy samples. These results are highly encouraging and suggest that the iKnife could be used in the clinic to provide a POC diagnosis.
Phelps DL, Borley J, Brown R, et al., 2022, The use of biomarkers to stratify surgical care in women with ovarian cancer, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 129, Pages: E66-E74, ISSN: 1470-0328
Saggu R, Barlow P, Butler J, et al., 2022, Considerations for mulitmodal prehabilitation in women with gynaecological cancers: a scoping review using realist principles, BMC Women's Health, Vol: 22, Pages: 1-35, ISSN: 1472-6874
Background: There is increasing recognition that prehabilitation is important as a means of preparing patients physically and psychologically for cancer treatment. However, little is understood about the role and optimal nature of prehabilitation for gynaecological cancer patients, who usually face extensive and life-changing surgery in addition to other treatments that impact significantly on physiological and psychosexual wellbeing. Review question: This scoping review was conducted to collate the research evidence on multimodal prehabilitation in gynaecological cancers and the related barriers and facilitators to engagement and delivery that should be considered when designing a prehabilitation intervention for this group of women. Methods: Seven medical databases and four grey literature repositories were searched from database inception to September 2021. All articles, reporting on multimodal prehabilitation in gynaecological cancers were included in the final review, whether qualitative, quantitative or mixed-methods. Qualitative on unimodal interventions were also included, as these were thought to be more likely to include information about barriers and facilitators which could also be relevant to multimodal interventions. A realist framework of context, mechanism and outcome was used to assist interpretation of findings. Results: In total, 24 studies were included in the final review. The studies included the following tumour groups: ovarian only (n=12), endometrial only (n=1), mixed ovarian, endometrial, vulvar (n=5) and non-specific gynaecological tumours (n=6). There was considerable variation across studies in terms of screening for prehabilitation, delivery of prehabilitation and outcome measures. Key mechanisms and contexts influencing engagement with prehabilitation can be summarised as: 1) The role of healthcare professionals and organisations 2) Patients’ perceptions of acceptability 3) Factors influencing patient motivation 4) Prehabilita
Kasaven L, Jones BP, Ghaem-Maghami S, et al., 2022, Study protocol for a randomised controlled trial on the use of intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy (UGLOC) as a method of fertility preservation in the management of benign ovarian cysts, BMJ Open, Vol: 12, ISSN: 2044-6055
Introduction: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the united kingdom (UK) is 5-10%. Despite minimally invasive surgical techniques, evidence suggests a number of healthy ovarian follicles and tissues are resected intraoperatively, resulting in subsequent decline of ovarian reserve. As such, there is an increasing demand for the implementation of fertility preservation surgery (FPS). This study will evaluate the effect on ovarian reserve following two different surgical interventions for the management of benign ovarian cysts. Methods and analysis: We will conduct a two-armed randomised controlled trial comparing laparoscopic ovarian cystectomy, considered gold standard treatment as per the Royal College of Obstetricians and Gynaecologists (RCOG) Green Top guidelines for the management of benign ovarian cysts, with ultrasound guided laparoscopic ovarian cystectomy (UGLOC), a novel method of FPS. The study commencement date was October 2021 and completion date October 2024. The primary outcome will be the difference in anti-Mullerian hormone (pmol/L) (AMH) and antral follicle count (AFC) measured 3 and 6 months post operatively from the pre-operative baseline. Secondary outcomes include assessment of various surgical and histopathological outcomes including: duration of hospital stay (days), duration of surgery (mins), presence of intra-operative cyst rupture (yes/no), presence of ovarian tissue within the specimen (yes/no) and the grade of follicles excised with specimen (grade 0-4). We aim to randomise 94 patients over 3 years to achieve power of 80% at an alpha level of 0.05.Ethics and dissemination: Findings will be published in peer reviewed journals and presented at national and international conferences and scientific meetings. The Chelsea NHS Research and Ethics Committee have awarded ethical approval of the study (21/LO/036).Trial registration number: NCT05032846
Kasaven L, Jones B, Saravelos S, et al., 2022, Reproductive outcomes in women with Borderline Ovarian Tumours. Does fertility treatment increase the risk of disease recurrence?, 38th Hybrid Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: I113-I113, ISSN: 0268-1161
Taylor A, Sundar SS, Bowen R, et al., 2022, British Gynaecological Cancer Society Recommendations for Women With Gynecological Cancer Who Received Non-standard Care During the COVID-19 Pandemic, OBSTETRICAL & GYNECOLOGICAL SURVEY, Vol: 77, Pages: 156-157, ISSN: 0029-7828
Taylor A, Sundar SS, Bowen R, et al., 2022, British Gynaecological Cancer Society Recommendations for Women With Gynecological Cancer Who Received Non-standard Care During the COVID-19 Pandemic, Obstetrical & Gynecological Survey, Vol: 77, Pages: 156-157, ISSN: 0029-7828
<jats:p>(Abstracted from <jats:italic toggle="yes">Int J Gynecol Cancer</jats:italic> 2022;32:9–14)</jats:p> <jats:p>Because of the overwhelming pressure placed on the health care system during the COVID-19 pandemic, resource prioritization and infection risk led to deviation from standard of care treatment for women with gynecologic cancer. The loss of intensive care availability, surgical capacity, as well as radio- and systemic therapy availability particularly impacted this vulnerable population.</jats:p>
Harter P, Sehouli J, Vergote I, et al., 2022, Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer (vol 385, pg 2123, 2021), NEW ENGLAND JOURNAL OF MEDICINE, Vol: 386, Pages: 704-704, ISSN: 0028-4793
Tabiri S, Kamarajah SK, Nepogodiev D, et al., 2022, Impact of Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection, BJS Open, Vol: 5, ISSN: 2474-9842
Harter P, Sehouli J, Vergote I, et al., 2021, Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 2123-2131, ISSN: 0028-4793
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- Citations: 93
Manchanda R, Oxley S, Ghaem-Maghami S, et al., 2021, COVID-19 and the impact on gynecologic cancer care, INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, Vol: 155, Pages: 94-101, ISSN: 0020-7292
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- Citations: 7
Rockall A, Barwick T, Wilson W, et al., 2021, Diagnostic accuracy of FEC-PET/CT, FDG-PET/CT and diffusion-weighted MRI in detection of nodal metastases in surgically treated endometrial and cervical carcinoma, Clinical Cancer Research, Vol: 27, Pages: 6457-6466, ISSN: 1078-0432
Purpose:Pre-operative nodal staging is important for planning treatment in cervical cancer (CC) and endometrial cancer (EC) but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-Fluoro-deoxy-glucose-(FDG)-PET/CT and diffusion-weighted-MRI (DW-MRI) with conventional morphological MRI.Experimetal Design:A prospective, multicentre observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centres. FEC-PET/CT, FDG-PET/CT and DW-MRI were compared to nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable CC stage=>1B1 or EC (grade 3 any stage with myometrial invasion or grade 1-2 stage=>II). Results:Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT, and 60 underwent FEC-PET/CT. 267 nodal regions in 118 women were strictly correlated at histology (nodal positivity rate 25%). Sensitivity per-patient (n=118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT were 40%*, 53%, 53%, 63%* and 67% for all cases (*p=0.016); 10%, 10%, 20%, 30% and 25% in CC (n=40); 65%, 75%, 70%, 80% and 88% in EC (n=78). FDG-PET/CT outperformed nodal size (p=0.006) and size ratio (p=0.04) for per-region sensitivity. False positive rates were all <10%. Conclusions:All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different to other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.
Jones BP, Saso S, Yazbek J, et al., 2021, Uterine Transplantation Scientific Impact Paper No. 65 April 2021, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 128, Pages: E51-E66, ISSN: 1470-0328
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- Citations: 5
Ahmed-Salim Y, Saso S, Meehan H, et al., 2021, A novel application of calcium electroporation to cutaneous manifestations of gynaecological cancer, European Journal of Gynecological Oncology, Vol: 42, Pages: 662-672, ISSN: 0392-2936
Introduction: Calcium electroporation (CaEP) is a new technique whereby intracellular concentrations of calcium are elevated by transient permeabilisation of the cell membrane using high-voltage electrical pulses. Tumour necrosis is induced with little damage to healthy tissue. Within gynaecological cancer, vulval cancer and vulval intraepithelial neoplasia (VIN) pose challenges for treatment, given the high recurrence rate, persistent symptoms and repeated resections required. In certain cases, CaEP may provide a suitable alternative.Methods: We present a case series of six patients with recurrent vulval squamous cell carcinoma(n=2), VIN III (n=2) and metastatic ovarian cancer (n=2), five of whom were treated with CaEP. This is the first known application of CaEP to gynaecological cancers .Results: The median follow-up time was 14 months (range 2-18 months). Within the cohort of patients, CaEP was applied a total of 10 times, achieving a complete response five times and partial response four times. Symptoms improved within six weeks for eight episodes following CaEP application. Beyond six weeks, symptoms eventually recurred in all patients and four patients required more than one CaEP procedure. CaEP was useful for palliation of distressing symptoms in one case of metastatic ovarian cancer. No intra-operative or post-operative complications have been reported to date. Conclusion: CaEP may be a promising short-term treatment in selected patients with recurrent VIN and vulval cancer, where other treatments had failed. If validated, it could provide an acceptable alternative where surgery is unacceptable. Long term follow-up is required to evaluate effects on recurrence.
Jones BP, Kasaven L, Vali S, et al., 2021, Uterine Transplantation: Review of Livebirths and Reproductive Implications, TRANSPLANTATION, Vol: 105, Pages: 1695-1707, ISSN: 0041-1337
Marcus D, King A, Yazbek J, et al., 2021, Anxiety and stress in women with suspected endometrial cancer: Survey and paired observational study, Psycho-Oncology: journal of the psychological, social and behavioral dimensions of cancer, Vol: 30, Pages: 1939-1400, ISSN: 1057-9249
ObjectiveTo determine the anxiety and stress levels of women with suspected endometrial cancer and factors affecting this.MethodsProspective survey and paired observational study of consecutive women with suspected endometrial cancer in a rapid access gynaecology clinic. Structured questionnaire including a GAD-7 anxiety test and a modified stress thermometer were used. Patients ranked their perception of a cancer diagnosis on 0-5 Likert scale (0 = confident not cancer and 5 = cancer). Patients requiring an endometrial tissue biopsy were asked to rank their pain on a visual analogue scale (VAS), this was paired with the survey results.Results250 patients completed the study and 23 of which underwent an endometrial tissue biopsy. The median age was 50-59 years old and 59% of women spoke English as their first language. 32% of patients had significant levels of anxiety with GAD-7 score ≥10. The median stress score was three out of five on Likert scale. GAD-7 anxiety scores were higher in women who perceived that they received insufficient information prior to clinic (sufficient information 5 vs. insufficient information 9.5, P = 0.00036) or had a disability (disability 9 vs. no disability 5.5, P = 0.00374). The median VAS score from the biopsies was seven out of 10 (range 1-10). Patients with higher anxiety levels (GAD-7 scores) were more likely to believe they had cancer P <0.00001.ConclusionsThese findings confirm high levels of anxiety and stress in women with suspected endometrial cancer. Adequate pre-clinic information is essential, particularly for minority groups.
COVIDSurg Collaborative Co-authors, 2021, Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score, British Journal of Surgery, Vol: 108, Pages: 1274-1292, ISSN: 0007-1323
Since the beginning of the COVID-19 pandemic tens of millions of operations have been cancelled1 as a result of excessive postoperative pulmonary complications (51.2 per cent) and mortality rates (23.8 per cent) in patients with perioperative SARS-CoV-2 infection2. There is an urgent need to restart surgery safely in order to minimize the impact of untreated non-communicable disease.As rates of SARS-CoV-2 infection in elective surgery patients range from 1–9 per cent3–8, vaccination is expected to take years to implement globally9 and preoperative screening is likely to lead to increasing numbers of SARS-CoV-2-positive patients, perioperative SARS-CoV-2 infection will remain a challenge for the foreseeable future.To inform consent and shared decision-making, a robust, globally applicable score is needed to predict individualized mortality risk for patients with perioperative SARS-CoV-2 infection. The authors aimed to develop and validate a machine learning-based risk score to predict postoperative mortality risk in patients with perioperative SARS-CoV-2 infection.
Marcus D, Yongue G, Shen Y, et al., 2021, Do delays to surgery influence survival in endometrial cancer?, Publisher: WILEY, Pages: 69-69, ISSN: 1470-0328
Keefe D, 2021, Fertility Treatment and Cancers-The Eternal Conundrum: A Systematic Review and Meta-analysis, OBSTETRICAL & GYNECOLOGICAL SURVEY, Vol: 76, Pages: 343-344, ISSN: 0029-7828
Ahmed-Salim Y, Galazis N, Bracewell-Milnes T, et al., 2021, The application of metabolomics in ovarian cancer management: a systematic review, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 754-774, ISSN: 1048-891X
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Allott L, Amgheib A, Barnes C, et al., 2021, Radiolabelling an F-18 biologic via facile IEDDA "click" chemistry on the GE FASTLab (TM) platform, Reaction Chemistry and Engineering, Vol: 6, Pages: 1070-1078, ISSN: 2058-9883
The use of biologics in positron emission tomography (PET) imaging is an important area of radiopharmaceutical development and new automated methods are required to facilitate their production. We report an automated radiosynthesis method to produce a radiolabelled biologic via facile inverse electron demand Diels–Alder (IEDDA) “click” chemistry on a single GE FASTLab™ cassette. We exemplified the method by producing a fluorine-18 radiolabelled interleukin-2 (IL2) radioconjugate from a trans-cyclooctene (TCO) modified IL2 precursor. The radioconjugate was produced using a fully automated radiosynthesis on a single FASTLab™ cassette in a decay-corrected radiochemical yield (RCY, d.c.) of 19.8 ± 2.6% in 110 min (from start of synthesis); the molar activity was 132.3 ± 14.6 GBq μmol−1. The in vitro uptake of [18F]TTCO-IL2 correlated with the differential receptor expression (CD25, CD122, CD132) in PC3, NK-92 and activated human PBMCs. The automated method may be adapted for the radiosynthesis of any TCO-modified protein via IEDDA chemistry.
Barcroft JF, Galazis N, Jones BP, et al., 2021, Fertility treatment and cancers-the eternal conundrum: a systematic review and meta-analysis., Human Reproduction, Vol: 36, Pages: 1093-1107, ISSN: 0268-1161
STUDY QUESTION: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer? SUMMARY ANSWER: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer. WHAT IS KNOWN ALREADY: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious. STUDY DESIGN, SIZE, DURATION: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences
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