Oncology

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Maintenance capecitabine plus ramucirumab after first-line chemotherapy in patients with advanced esophagogastric adenocarcinoma: results from the randomized PLATFORM study
(American Society of Clinical Oncology, 2025-04-25) Gordon, Anderley; Cunningham, David; Rajan, Zayn; Fong, Caroline; Peckitt, Clare; Satchwell, Laura; Cromarty, Susan; Kidd, Shannon; Piadel, Katarzyna; Leamon, Becky; Zhitkov, Oleg; Davidson, Michael; Thompson, Joyce; Maisey, Nicholas; Darby, Suzanne; Waddell, Tom; Morgan, Carys; Bradshaw, Alexander; Petty, Russell; Fribbens, Charlotte; Rao, Sheela; Starling, Naureen; Chau, Ian; Royal Marsden Hospital; University Hospitals Birmingham NHS Foundation Trust; Guys Hospital; Weston Park Cancer Centre; The Christie NHS Foundation Trust; Velindre Cancer Centre; Northern Centre for Cancer Care; University of Dundee; Oncology; Medical and Dental; Thompson, Joyce
Purpose: PLATFORM is an adaptive phase II study assessing maintenance therapies in advanced esophagogastric adenocarcinoma (OGA). We evaluated the role of capecitabine plus a vascular endothelial growth factor receptor 2 inhibitor ramucirumab (cape-ram) in these patients. Methods: Human epidermal growth factor receptor 2 (HER2)-negative patients with advanced OGA with stable or responding disease after 18 weeks of induction platinum-based chemotherapy were randomly assigned 1:1 to surveillance or cape-ram. The primary end point was progression-free survival (PFS), and key secondary end points were overall survival (OS) and safety. Recruitment to the cape-ram arm closed prematurely because of industry support withdrawal. A one-sided log-rank test with a 2.5% significance level was considered significant. Results: Between April 2019 and November 2022, 25 surveillance and 22 cape-ram patients were contemporaneously randomly assigned. Median follow-up was 24.4 months. Compared with surveillance, cape-ram significantly prolonged PFS (hazard ratio [HR], 0.33 [95% CI, 0.17 to 0.63], P < .001; median PFS: 2.5 months with surveillance versus 5.5 months with cape-ram; 6-month PFS rate: 4% [95% CI, 0.3% to 17.0%] v 42.9% [95% CI, 21.9% to 62.3%], respectively) and OS (HR, 0.51 [95% CI, 0.26 to 1.00], P = .023; median OS: 7.1 months with surveillance v 14.4 months with cape-ram; median OS from start of induction chemotherapy was 12.1 months v 19.5 months, respectively). Of 10 cape-ram patients with measurable disease, 1 had an incremental partial response. Grade ≥3 adverse events (AEs) were seen in 32% surveillance and 57% cape-ram patients. Six cape-ram patients had grade 3 treatment-related AEs, and no new safety signals were identified. Conclusion: Maintenance cape-ram after induction chemotherapy for patients with HER2-negative OGA significantly improved survival compared with surveillance. To our knowledge, this is the first randomized maintenance study demonstrating survival benefit and provides support for maintenance treatment
Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.
(Elsevier, 2020-01-23) Grist, James T; Withey, Stephanie; MacPherson, Lesley; Oates, Adam; Powell, Stephen; Novak, Jan; Abernethy, Laurence; Pizer, Barry; Grundy, Richard; Bailey, Simon; Mitra, Dipayan; Arvanitis, Theodoros N; Auer, Dorothee P; Avula, Shivaram; Peet, Andrew C
The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.
Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.
(Wiley, 2020-11-18) Tseng, William W; Barretta, Francesco; Conti, Lorenzo; Grignani, Giovanni; Tolomeo, Francesco; Albertsmeier, Markus; Angele, Martin K; Rutkowski, Piotr; Skoczylas, Jacek; De Paoli, Antonino; Navarria, Federico; Raut, Chandrajit P; Fairweather, Mark; Farma, Jeffrey M; Nessim, Carolyn; Goel, Neha; Grignol, Valerie P; Ford, Samuel J; Cardona, Kenneth; Subhawong, Ty; Tattersall, Hannah L; Lee, Rachel M; Hu, James S; von Mehren, Margaret; Sanfilippo, Roberta; Gronchi, Alessandro; Surgery; Medical and Dental; Ford, Samuel
Background: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. Methods: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. Results: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. Conclusions: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.
A review of retroperitoneal liposarcoma genomics.
(Elsevier, 2020-03-28) Tyler, Robert; Wanigasooriya, Kasun; Taniere, Philippe; Almond, Max; Ford, Samuel; Desai, Anant; Beggs, Andrew; Surgery; Medical and Dental; Almond, Max; Ford, Samuel; Desai, Anant
Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting.
A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR).
(BioMed Central, 2020-06-12) O'Cathail, Séan M; Davis, Steven; Holmes, Jane; Brown, Richard; Fisher, Kerry; Seymour, Leonard; Adams, Richard; Good, James; Sebag-Montefiore, David; Maughan, Tim; Hawkins, Maria A; Oncology; Medical and Dental; Good, James
Background: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for 'proof-of-concept' and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019.
Association of gastric acid suppression and sorafenib efficacy in advanced hepatocellular carcinoma.
(Wolters Kluwer Health, 2021-02-01) Razak, Razwan A; Fletcher, Peter; Kunene, Victoria; Ma, Yuk Ting; Oncology; Medical and Dental; Kunene, Victoria; Ma, Yuk Ting
Background: Recent studies have revealed that coadministration of gastric acid suppressants reduces the efficacy of the tyrosine kinase inhibitors erlotinib and sunitinib in patients with non-small cell lung cancer and renal cell carcinoma, respectively. The authors have therefore assessed if the concurrent use of gastric acid suppressants and sorafenib impairs outcomes in patients with advanced hepatocellular carcinoma (HCC). Methods: A retrospective analysis was conducted on all patients treated with sorafenib for advanced HCC at a single tertiary referral unit in the United Kingdom, between January 2008 and January 2014. A multivariate Cox proportional hazard model was used to assess the effect of the concomitant use of gastric acid suppression and sorafenib on progression-free survival (PFS) and overall survival (OS). Results: Data were collected from 197 patients, of which 182 could be assessed for this study; 77 (42%) were on concurrent gastric acid suppression therapy. After adjusting for imbalances between the groups, a Cox regression analysis gave an adjusted hazard ratio for the concurrent acid suppression group compared with the no acid suppression group of 5.4 (95% confidence interval, 3.6-7.9) for PFS and 1.85 (95% confidence interval, 1.3-2.6) for OS. Conclusions: This single-center experience shows that patients with advanced HCC taking sorafenib and concomitant gastric acid suppression therapy have significantly inferior PFS and OS. This is the first time that this negative interaction has been reported and further prospective validation is warranted.
Achieving 'marginal gains' to optimise outcomes in resectable pancreatic cancer.
(MDPI, 2021-04-01) Powell-Brett, Sarah; Pande, Rupaly; Roberts, Keith J; Liver; Liver surgery; Medical and Dental; Powell-Brett, Sarah; Pande, Rupaly; Roberts, Keith J
Improving outcomes among patients with resectable pancreatic cancer is one of the greatest challenges of modern medicine. Major improvements in survival will result from the development of novel therapies. However, optimising existing pathways, so that patients realise benefits of already proven treatments, presents a clear opportunity to improve outcomes in the short term. This narrative review will focus on treatments and interventions where there is a clear evidence base to improve outcomes in pancreatic cancer, and where there is also evidence of variation and under-treatment. Avoidance of preoperative biliary drainage, treatment of pancreatic exocrine insufficiency, prehabiliation and enhanced recovery after surgery, reducing perioperative complications, optimising opportunities for elderly patients to receive therapy, optimising adjuvant chemotherapy and regular surveillance after surgery are some of the strategies discussed. Each treatment or pathway change represents an opportunity for marginal gain. Accumulation of marginal gains can result in considerable benefit to patients. Given that these interventions already have evidence base, they can be realised quickly and economically.
A timely oral option: single-agent vinorelbine in Desmoid tumors
(Oxford University Press, 2020-10-02) Gennatas, Spyridon; Chamberlain, Florence; Smrke, Alannah; Stewart, James; Hayes, Andrew; Roden, Lorna; Messiou, Christina; Kowa, Jie-Ying; Estival, Anna; Chauhan, Dharmisha; Thway, Khin; Fisher, Cyril; van der Graaf, Winette T A; Jones, Robin L; Benson, Charlotte; Cellular pathology; Medical and Dental; Fisher, Cyril
Introduction: Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine. Materials and methods: A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed. Results: A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%). Conclusion: Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.
Promoting equitable genetic testing in ovarian cancer : the demonstration of improvement for molecular ovarian cancer testing (DEMO) project
(BMJ Publishing Group, 2025-02-25) Leung, Elaine Yl; Funingana, Ionut Gabriel; Bird, Lisa; Alcaraz, Marie-Lyne; Evans, Anuji; Considine, Anna; Freeman, Susan; Jimenez-Linan, Mercedes; Spencer, Catherine; Phanasan, Kiran; Winning, Julie; Ang, Joo Ern; Parkinson, Christine; Ong, Kai Ren; Butler, Samantha; Ridgway, Oliver; Charles, Ian; Pannell, Rachel; Abedin, Parveen; Boyle, William; Emery, Jamie; Salter-Scott, Jayne; Williams, Sarah; Ganesan, Raji; Sundar, Sudha; Balega, Janos; Brenton, James D; University of Birmingham; Cancer Research UK Cambridge Institute; Birmingham Women's Hospital; Sandwell and West Birmingham NHS Trust; et al.; Gynaecological Oncology; Communications; Patient Experience; Oncology; Admin and Clerical; Medical and Dental; Nursing and Midwifery Registered; Evans, Anuji; Spencer, Catherine; Phanasan, Kiran; Charles, Ian; Pannell, Rachel; Emery, Jamie; Salter-Scott, Jayne; Sundar, Sudha; Balega, Janos; Williams, Sarah
Parallel genetic testing (testing for both tumour and germline gene changes) after the diagnosis of ovarian cancer should be considered the standard of care and is crucial to support treatment decisions. The demonstration of improvement for molecular ovarian cancer testing (DEMO) project aimed to develop patient-focused tools to promote equitable genetic care in diverse communities with high proportions of patients with limited English proficiency and biopsy guidelines to address the variations in specimen quality in different geographical regions in the UK. Our three work packages (WP) aimed to promote awareness by addressing the information gaps in different community groups (WP1), develop infrastructure to evaluate the different tissue collection pathways in different regions (WP2) and support continuing professional development (CPD) to encourage best practices with the involvement of patients (WP3). Our output included a multimedia multilanguage information package with paired National Health Service-branded written materials to support genetic testing after ovarian cancer diagnosis (https://ovarian.org.uk/demo-uk/), a scalable database to enable a multisite audit of parallel genetic testing pathways and a collection of CPD events that had patient involvement as an essential component. In addition, we have collaborated with patient and community groups to contribute to a national consensus guidance on genetic testing in ovarian cancer. Our co-production work has been recognised by local and regional awards as an exemplar for patient and public involvement (PPI). This has supported the start of a legacy co-production group in gynaeoncology (https://www.dhlnetwork.com/gohildas) to address the critical unmet need for sustainable and equity-oriented PPI to advocate for underserved communities. The DEMO project has contributed to raising awareness of the importance of equitable genetic care in ovarian cancer. We will continue to build on this groundwork to support future quality improvement projects and research, with the ultimate goal of improving the outcomes of patients with ovarian cancer.
Functional analysis of fibroblasts and macrophages in head and neck paragangliomas.
(Lausanne : Frontiers Research Foundation, 2024-11-15) Baruah, Paramita; Marshall, Jennifer L; Nefla, Meriam; Pucino, Valentina; Adams, Holly; Turner, Jason D; Gilbert, Sebastian; Powell, Emily; Neag, Georgiana; Monksfield, Peter; Irving, Richard M; Croft, Adam P; Dumitriu, Ingrid E; Buckley, Christopher D; ENT; Medical and Dental; Monksfield, Peter; Irving, Richard
Background and aim: Head and neck paragangliomas (HNPGN) are tumours that carry significant morbidity The role of the stroma in the pathogenesis of HNPGN is not completely understood. This study explores the profile of fibroblasts and macrophages in HNPGN. Methods: Ten patients undergoing HNPGN surgery were recruited. CD68 and CD163 immunohistochemistry was performed for macrophage analysis; CD90 and podoplanin (PDPN) expression was examined to identify fibroblasts. RT-qPCR was performed on HNPGN tissue for macrophage- and fibroblast-associated molecules. Fibroblast cultures were established from HNPGN were analysed by RT-qPCR and flowcytometry. Confocal microscopy for MCT1 and MCT4 was performed in HNPGN. Results: CD68 and CD163 expressing macrophages were noted in HNPGN. CD90 and PDPN expressing cells were present in HNPGN. RT-qPCR analysis showed expression of phenotypic and functional macrophage- and fibroblast-associated molecules in HNPGN. RT-qPCR analysis of fibroblasts cultured from HNPGN confirmed the expression of several molecules including PDPN at comparable levels to healthy tissue fibroblasts. Expression of FAP, MCT-1, insulin receptor (CD220) and insulin growth factor receptor-2 (CD222) was noted on HNPGN derived fibroblasts on flowcytometry. MCT1 and MCT4 were expressed in HNPGN tumour cells and stromal macrophages in-situ. Conclusion: Fibroblasts and macrophages are present in the HNPGN tumour microenvironment, and several macrophage and fibroblast functional markers are expressed in HNPGN. Macrophages in HNPGN tissue express metabolic markers MCT1 and MCT4. Further analysis of the fibroblast and macrophage function in HNPGN will improve our understanding of their potential roles in tumour pathogenesis.
A systematic review of adult pineoblastoma
(Frontiers Research Foundation, 2024-12-16) Chu, Xiufeng; Zhang, Ting; Benghiat, Helen; Xu, Jixuan; Oncology; Medical and Dental; Benghiat, Helen
Background: Adult pineoblastoma is an extremely rare central nervous system malignancy. Limitations of tumour databases, single institution retrospective analyses and a few case reports are not sufficient to clarify treatment options. Therefore, a systematic review of comprehensive research data provides referenceable treatment options. Methods: A systematic review was performed using MEDLINE and Embase using the terms "pineoblastoma" and "adult". Relevant articles in the references were considered to supplement this systematic review. In addition, data were analysed using Kaplan-Meier survival curves, COX analysis, chi-square tests and log-rank tests. Results: A total of 108 adult cases from 32 articles were included in this study and the median age at diagnosis was 30 years. The 5-year survival rate was 49.5% (95% confidence interval: 0.378-0.602) and the 10-year survival rate was 33.9% (95% confidence interval: 0.207-0.476). During the 10-year follow-up period, Kaplan-Meier survival curves highlighted that the gross total resection was more beneficial than subtotal resection and no surgery (P=0.018). The treatment modality of radiotherapy and chemotherapy was beneficial for survival (P<0.001; P=0.020). In addition, multivariate COX analysis showed that radiotherapy was an independent factor in the beneficial prognosis (P<0.001) and gross total resection tends to improve survival within five years (P=0.079). Conclusion: For adult pineoblastoma, gross total excision and radiotherapy can be beneficial for survival.Systematic Review Registration: [website], identifier [registration number].
Development of a conceptual framework for an electronic patient-reported outcome (ePRO) system measuring symptoms and impacts of CAR T-cell therapies in patients with haematological malignancies.
(Lancet Pub. Group, 2024-10-25) Khatsuria, Foram; McMullan, Christel; Aiyegbusi, Olalekan Lee; Shaw, Karen L; Iqbal, Roshina; Kinsella, Francesca; Wilson, Keith; Pyatt, Lester; Lewis, Marlene; Wheldon, Sophie M R; Burns, David; Chakraverty, Ronjon; Calvert, Melanie; Hughes, Sarah E
Chimeric antigen receptor (CAR) T-cell therapy is associated with potentially severe toxicities that create a substantial burden for patients. Patient-reported outcomes (PROs) offer valuable insights into symptoms, functioning, and other complex constructs of interest. In this Review, we aimed to identify symptom and impact concepts important to patients receiving CAR T-cell therapy, construct a conceptual framework for an electronic patient-reported outcome (ePRO) system, and identify timepoints to capture PRO data for CAR T-cell therapies. We searched MEDLINE (OVID) and Web of Science (Clarivate) for articles in English published from Aug 30, 2017, to March 2, 2023. No restrictions on study design were applied. 178 symptoms or constructs were extracted from 44 articles reporting PRO collection in adults with haematological malignancies receiving CAR T-cell therapy. Six health-care professionals and 11 patients and caregiver partners verified construct relevance to clinical management and lived experience, respectively. 109 constructs were sorted according to the four domains of conceptual framework: symptom burden, impact of disease and treatment, tolerability, and health-related quality of life. The identification of concepts beyond symptom burden underscores the importance of PRO measurement for long-term monitoring, to align outcomes with patient concerns. The framework will facilitate PRO measure selection for systematic gathering of PROs from individuals with haematological malignancies receiving CAR T-cell therapies.
Cancer and COVID-19: on the quest for effective vaccines
(American Association for Cancer Research, 2020-12-17) Kwok, Marwan; Fritsch, Edward F; Wu, Catherine J; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Dana-Farber Cancer Institute; Broad Institute of MIT and Harvard; Harvard Medical School; Brigham and Women's Hospital
Cancer vaccine development has been historically fraught with difficulty, but tremendous progress has been made over the past 5 years. In this In Focus article, we reflect on the progress and challenges with vaccine development for cancers in general and for hematologic malignancies in particular, and suggest how our cancer vaccine experience can offer insight into COVID-19 vaccination.
Buried bumper syndrome: a rare complication during radical chemoradiotherapy for head and neck cancer
(BMJ Publishing Group, 2024-01-24) Teo, Rachel Pei Jing; Maniam, Akash; Boon, Ian; Boon, Cheng S; University Hospitals Birmingham NHS Foundation Trust; Eastern Regional Health Authority, Trinidad and Tobago; Leeds Cancer Research UK Centre; Worcestershire Acute Hospitals NHS Trust
Patients undergoing radical treatment particularly chemoradiotherapy for cancer of the upper aerodigestive tract frequently experience progressive deterioration in swallow during and immediately after treatment. It is important to identify patients at high risk of compromised feeding early, following diagnosis, so that alternate feeding routes, such as percutaneous endoscopic gastrostomies (PEGs), can be promptly and prophylactically instituted, in keeping with the UK Head and Neck Cancer Guidelines (2016).
Systematic review and meta-analysis: taurine and its association with colorectal carcinoma
(John Wiley & Sons Ltd, 2024-12-13) Sinha, Akshat; Griffith, Liam; Acharjee, Animesh
Background: Colorectal cancer (CRC) is one of the most common cancers. Various options are available for treatment, but prognosis is still poor in the more advanced stages. Current screening methods are not as accurate for distinguishing between benign and malignant growths, resulting in unnecessary invasive procedures. Recently a focus has been placed on identifying metabolites. Of these, taurine has frequently been detected, and this particular compound has a multifactorial role in human physiology. Methods: We conducted a systematic review of studies up till November 2023. Searches were done in three databases- MEDLINE, CINAHL-Ebsco, and PubMed. Three independent reviewers filter titles, abstracts, and full-texts according to selection criteria. Ten studies (samples = 1714) were identified showing a differential level of taurine in CRC patient samples. Quality assessment accounted for the risk of bias of each study using the 'robvis' tool. Where meaningful comparisons could be made, meta-analyses were carried out using the 'R' program for precalculated effect sizes with 'metagen' in R. The 'meta' package was utilised for creation of forest plots. Findings: Taurine was shown to significantly increase odds of CRC. It was also significantly associated with being a discriminator for CRC as a diagnostic metabolite. This was maintained at various stages of CRC. Taurine had increased expression in CRC patients, especially when the matrix utilised was blood. Nevertheless, there was significant heterogeneity for some outcomes. Interpretation: In conclusion, these findings highlight the potential of using taurine as well as other bile acid metabolites (lithocholic and ursodeoxycholic acid) to diagnose CRC and illustrate the link with microbiome interactions. Overall increased taurine concentration are associated with significantly increased odds for CRC. There was mostly an increase in relative expression of taurine in CRC samples, excluding results from Wang et al.
PTPN9 regulates HER3 phosphorylation during trastuzumab treatment and loss of PTPN9 is a potential biomarker for trastuzumab resistance in HER2 positive breast cancer
(Wiley, 2024-11-24) Azad, Abul; Arshad, Maryam; Generali, Daniele; Feldinger, Katharina; Gijsen, Merel; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Leek, Russell; Haider, Syed; Kellokumpu-Lehtinen, Pirkko-Liisa; Roxanis, Ioannis; Harris, Adrian Llewellyn; Shaaban, Abeer Mahmoud; Joensuu, Heikki; Kong, Anthony; Histopathology; Medical and Dental; Shaaban, Abeer Mahmoud
No abstract available
Microbiome-based colon cancer patient stratification and survival analysis.
(John Wiley & Sons Ltd, 2024-11-13) Smyth, Joshua; Godet, Julien; Choudhary, Anisa; Das, Anubrata; Gkoutos, Georgios V; Acharjee, Animesh
Background: Colorectal cancer (CRC) is any cancer that starts in the colon or the rectum and presents a significant health concern. It is the third most diagnosed and the second deadliest cancer, with an estimated 153,020 new cases and 52,550 deaths in 2023. The severity of colon cancer may be attributed to its ability to avoid the host immune system and growth suppressors, its asymptomatic nature in the early stages, its association with a continually ageing population and unfavourable diet and obesity. The composition of the gut microbiome plays an important role in the development of CRC and presents as an important target in early detection and in predicting treatment outcomes in CRC. This study aims to identify microbiome-specific derived clusters in CRC patients and conduct subsequent survival analysis using the specific microbiome features within clusters. Methods: Consensus clustering and feature selection, involving a Kruskal-Wallis test, a random forest and least absolute shrinkage and selection operator (LASSO) were applied resulting in the identification of differently expressed microbiomes between clusters. Lastly, survival analysis was performed on the selected features using Kaplan-Meier curves and Cox regression. K-means clustering, as selected using consensus clustering interpretation, presented three distinct clusters with clear differences in alpha and beta diversity and baseline clinical variables. Results: A total 1311 of the 1406 microbes were selected using the Kruskal Wallis and passed to the random forest and LASSO, which narrowed the dataset to 140 features. Following the survival analysis, eight microbiome species, namely N4likevirus, Ambidensovirus, Synechococcus, Thermithiobacillus, Hydrocarboniphaga, Rhodovibrio, Gloeobacter and Candidatus Nitrosotenuis, were selected as significant in clustering and survival. Conclusion: This study reveals the heterogeneity of the CRC microbiome and its effect on disease prognosis and necessitates further exploration of the biological mechanisms of these selected microbiomes as well further investigation of whether the approach depicted here is applicable to other cancer types.
Breast angiosarcoma surveillance study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall
(Oxford University Press, 2021-03-22) Banks, J; George, J; Potter, S; Gardiner, M D; Ives, C; Shaaban, A M; Singh, J; Sherriff, J; Hallissey, M T; Horgan, K; Harnett, A; Desai, A; Ferguson, D J; Tillett, R; Izadi, D; Sadideen, H; Jain, A; Gerrand, C; Holcombe, C; Hayes, A; Teoh, V; Wyld, L; Royal Devon and Exeter Hospital NHS Foundation Trust; University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust; North Bristol NHS Trust; Bristol Medical School; Frimley Health Foundation NHS Trust; University of Oxford; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Surrey and Sussex Healthcare NHS Trust; Leeds Teaching Hospitals NHS Trust; Norfolk and Norwich University Hospital NHS Foundation Trust; Imperial College London; Imperial College Healthcare NHS Trust; Royal National Orthopaedic Hospital NHS Trust; British Association of Plastic, Reconstructive and Aesthetic Surgeons; Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust; Royal Marsden Hospital; Histopathology; Oncology; General Surgery; Surgery; Medical and Dental; Shaaban, Abeer; Sherriff, Jenny; Hallissey, Mike; Desai, Anant
Background: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort. Methods: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres. Results: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort. Conclusion: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study.
Bortezomib, melphalan, dexamethasone: a new standard of care for AL amyloidosis?
(American Society of Clinical Oncology, 2020-08-04) Pratt, Guy; University Hospitals Birmingham NHS Foundation Trust; Haematology; Medical and Dental; Pratt, Guy
No abstract available
Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation
(Taylor & Francis, 2020-03-18) Saulite, Ieva; Ignatova, Desislava; Chang, Yun-Tsan; Fassnacht, Christina; Dimitriou, Florentia; Varypataki, Eleni; Anzengruber, Florian; Nägeli, Mirjam; Cozzio, Antonio; Dummer, Reinhard; Scarisbrick, Julia; Pascolo, Steve; Hoetzenecker, Wolfram; Bobrowicz, Malgorzata; Guenova, Emmanuella; University Hospital Zurich; University of Zurich; Cantonal Hospital St. Gallen; University Hospitals Birmingham NHS Foundation Trust; Kepler University Hospital; Medical University of Warsaw; Lausanne University Hospital CHUV; University of Lausanne; Dermatology; Medical and Dental; Scarisbrick, Julia
Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4+ T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4+ T cells from SS patients and to CD4+ cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor.

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