Imperial College London

Dr David L Phelps

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Clinical Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2125d.phelps

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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13 results found

Ahmed-Salim Y, Saso S, Meehan H, Galazis N, Phelps D, Jones B, Chan M, Chawla M, Lathouras K, Gabra H, Fotopoulou C, Ghaem-Maghami S, Smith JRet 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.

Journal article

Ahmed-Salim Y, Galazis N, Bracewell-Milnes T, Phelps DL, Jones BP, Chan M, Munoz-Gonzales MD, Matsuzono T, Smith JR, Yazbek J, Krell J, Ghaem-Maghami S, Saso Set 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

Journal article

Phelps DL, Saso S, Ghaem-Maghami S, 2020, Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies, BRITISH JOURNAL OF CANCER, Vol: 123, Pages: 1471-1473, ISSN: 0007-0920

Journal article

Phelps DL, Saso S, Ghaem-Maghami S, 2020, Analysis of worldwide surgical outcomes in COVID-19-infected patients: a gynecological oncology perspective, Future Science OA, Vol: 6, Pages: 1-8, ISSN: 2056-5623

Coronavirus Disease 2019 (COVID-19) guidance limits all but the most urgent surgery in the United Kingdom. We review the literature and our experience in gynecology to assess perioperative outcomes. PubMed was searched with (surg*[Title])AND(COVID[Title]), (surg*[Title])AND(2019-nCoV[Title]), and (surg*[Title])AND(SARS-CoV-2[Title]), and 67 COVID-19-positive surgical patients across ten hospitals in four countries are included. Median mortality was 33%. Cardiac and pulmonary co-morbidities associated with higher risk of COVID-19-positive postoperative death. Mortality was high in neurosurgery (80%) and the lowest in gynecological oncology surgery (none). This analysis provides an evidence base on which to consider surgical risk assessment for different specialties. Risk of perioperative death needs to be assessed in the context of patients’ co-morbidities and surgical specialty. An individualized approach toward surgical decision making is imperative.

Journal article

Phelps DL, Balog J, Gildea LF, Bodai Z, El-Bahrawy MA, Speller AVM, Rosini F, Kudo H, McKenzie JS, Brown R, Takats Z, Ghaem-Maghami Set al., 2018, The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS), British Journal of Cancer, Vol: 118, Pages: 1349-1358, ISSN: 0007-0920

BackgroundSurvival from ovarian cancer (OC) is improved with surgery, but surgery can be complex and tumour identification, especially for borderline ovarian tumours (BOT), is challenging. The Rapid Evaporative Ionisation Mass Spectrometric (REIMS) technique reports tissue histology in real-time by analysing aerosolised tissue during electrosurgical dissection.MethodsAerosol produced during diathermy of tissues was sampled with the REIMS interface. Histological diagnosis and mass spectra featuring complex lipid species populated a reference database on which principal component, linear discriminant and leave-one-patient-out cross-validation analyses were performed.ResultsA total of 198 patients provided 335 tissue samples, yielding 3384 spectra. Cross-validated OC classification vs separate normal tissues was high (97·4% sensitivity, 100% specificity). BOT were readily distinguishable from OC (sensitivity 90.5%, specificity 89.7%). Validation with fresh tissue lead to excellent OC detection (100% accuracy). Histological agreement between iKnife and histopathologist was very good (kappa 0.84, P < 0.001, z = 3.3). Five predominantly phosphatidic acid (PA(36:2)) and phosphatidyl-ethanolamine (PE(34:2)) lipid species were identified as being significantly more abundant in OC compared to normal tissue or BOT (P < 0.001, q < 0.001).ConclusionsThe REIMS iKnife distinguishes gynaecological tissues by analysing mass-spectrometry-derived lipidomes from tissue diathermy aerosols. Rapid intra-operative gynaecological tissue diagnosis may improve surgical care when histology is unknown, leading to personalised operations tailored to the individual.

Journal article

Marcus D, Savage A, Phelps D, Bodai Z, Rosini F, Kudo H, Takats Z, Ghaem-Maghami Set al., 2017, PROOF OF CONCEPT: CAN THE INTELLIGENT SURGICAL KNIFE DIAGNOSE ENDOMETRIAL CANCER?, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1152-1152, ISSN: 1048-891X

Conference paper

Phelps DL, Borley J, Flower K, Dina R, Darb-Esfahani S, Braicu I, Sehouli J, Fotopoulou C, Wilhelm-Benartzi CS, Gabra H, Yazbek J, Chatterjee J, Ip J, Khan H, Likos-Corbett MT, Brown R, Ghaem-Maghami Set al., 2017, Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study, British Journal of Cancer, Vol: 116, Pages: 1287-1293, ISSN: 1532-1827

BackgroundSurvival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.MethodsClinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.ResultsAltogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). ConclusionMYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.

Journal article

Chatterjee J, Dai W, Abd Aziz NH, Teo PY, Wahba J, Phelps DL, Maine CJ, Whilding L, Dina R, Trevisan G, Flower K, George A, Ghaem-Maghami Set al., 2016, Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer, Clinical Cancer Research, Vol: 23, Pages: 3453-3460, ISSN: 1557-3265

Purpose We aimed to establish whether PD-1 and PD-L1 expression, in ovarian cancer (OC) tumour tissue and blood, could be used as biomarkers for discrimination of tumour histology and prognosis of OC. Experimental Design Immune cells were separated from blood, ascites and tumour tissue obtained from women with suspected OC and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumour associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumours and epithelial ovarian cancers (EOC) - confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumour marker CA-125 alone. Plasma soluble PD-L1 was elevated in EOC patients compared to healthy women and patients with benign ovarian tumours. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti PD-1/PD-L1 therapy in ovarian cancer.

Journal article

Phelps DL, 2016, A tumour-DNA methylation biomarker to predict response to treatment in patients with ovarian cancer; a multi-centre study., Royal College of Obstetricians and Gynaecologists - World Congress

Conference paper

Doria ML, McKenzie JS, Mroz A, Phelps DL, Speller A, Rosini F, Strittmatter N, Golf O, Veselkov K, Brown R, Ghaem-Maghami S, Takats Zet al., 2016, Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging, Scientific Reports, Vol: 6, ISSN: 2045-2322

Ovarian cancer is highly prevalent among European women, and is the leading cause of gynaecological cancer death. Current histopathological diagnoses of tumour severity are based on interpretation of, for example, immunohistochemical staining. Desorption electrospray mass spectrometry imaging (DESI-MSI) generates spatially resolved metabolic profiles of tissues and supports an objective investigation of tumour biology. In this study, various ovarian tissue types were analysed by DESI-MSI and co-registered with their corresponding haematoxylin and eosin (H&E) stained images. The mass spectral data reveal tissue type-dependent lipid profiles which are consistent across the n = 110 samples (n = 107 patients) used in this study. Multivariate statistical methods were used to classify samples and identify molecular features discriminating between tissue types. Three main groups of samples (epithelial ovarian carcinoma, borderline ovarian tumours, normal ovarian stroma) were compared as were the carcinoma histotypes (serous, endometrioid, clear cell). Classification rates >84% were achieved for all analyses, and variables differing statistically between groups were determined and putatively identified. The changes noted in various lipid types help to provide a context in terms of tumour biochemistry. The classification of unseen samples demonstrates the capability of DESI-MSI to characterise ovarian samples and to overcome existing limitations in classical histopathology.

Journal article

Phelps DL, 2016, Malignant or Benign? - Diagnosis of pelvic mass histology using dried blood spot paper spray mass-spectrometry., Royal College of Obstetricians and Gynaecologists - World Congress

Conference paper

Phelps DL, Balog J, El-Bahrawy M, Speller A, Brown R, Takats Z, Ghaem-Maghami Set al., 2016, Diagnosis of borderline ovarian tumours by rapid evaporative ionisation mass spectrometry (REIMS) using the surgical intelligent knife (iKnife), Royal College of Obstetricians and Gynaecologists - Blair Bell Academic Meeting, Publisher: Wiley, Pages: e4-e4

Conference paper

Phelps DL, Rapid evaporative ionisation mass spectrometry (REIMS) iKnife identifies gynaecological tissue with excellent accuracy ex-vivo and in-vivo, American Society of Mass Spectrometry

Poster

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