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Publication Testing for t(3;8) in MYC/BCL6 re-arranged large B cell lymphoma identifies a high risk subgroup with inferior survival(American Society of Hematology, 2024-07-04) Maybury, Bernard D; James, Lisa J; Phillips, Neil; Venkatadasari, Indrani; Qureshi, Iman; Riley, James; Talbot, Georgina; Moosai, Shivir; Giles, Hannah; Chadderton, Nicola; Dowds, James; Rakesh, Pallav; Crosland, Henry; Haslam, Aidan; Lane, Sarah; Vega Gonzalez, Monica; Davies, David; Cherian, George; Shenouda, Amir; Kaudlay, Praveen; Starczynski, Jane; Rudzki, Zbigniew; Chaganti, Sridhar; University Hospitals Birmingham NHS Foundation Trust; University Hospitals of the North Midlands NHS Trust; The Royal Wolverhampton NHS Trust; University Hospitals Coventry and Warwickshire NHS Foundation Trust; The Dudley Group NHS Foundation Trust; Shrewsbury and Telford Hospital NHS Trust; Walsall Healthcare NHS Trust; Sandwell and West Birmingham Hospitals NHS Trust; Oncology/Cancer Services; Haematology; Pathology; Oncology; Gonzalez, Monica Vega; Maybury, Bernard Douglas; James, Lisa Jane; Giles, Hannah Victoria; Chadderton, Nicola; Dowds, James; Crosland, Henry; Haslam, Aidan; Rudzki, Zbigniew; Chaganti, Sridhar; Maybury, Bernard Douglas; James, Lisa Jane; Giles, Hannah Victoria; Chadderton, Nicola; Dowds, James; Crosland, Henry; Haslam, Aidan; Rudzki, Zbigniew; Chaganti, SridharA reciprocal t(3;8) BCL6::MYC fusion is common in large B cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double hit cases are not adverse, whereas t(3;8) negative MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.Publication Myc/Bcl6 double hit lymphoma negative for T(3;8) Bcl6::Myc fusion Is associated with inferior survival, in contrast with T(3;8) positive pseudo‐double hit lymphoma(Wiley, 2023-06) Maybury, B. D.; James, L.; Chadderton, N.; Dowds, J.; Venkatadasari, I.; Riley, J.; Qureshi, I.; Talbot, G.; Giles, H. V.; Phillips, N. J.; Gonzalez, M. Vega; Rakesh, P.; Haslam, A.; Davies, D.; Moosai, S.; Lane, S. A.; Shenouda, A.; Cherian, G. V.; Kaudlay, P. K.; Starczynski, J.; Rudzki, Z; Chaganti, S; University Hospitals Birmingham NHS Foundation Trust; The Royal Wolverhampton NHS Trust; Worcestershire Acute Hospitals NHS Trust; University Hospitals of North Midlands NHS Trust; Walsall Healthcare NHS Trust; The Dudley Group Foundation Trust; Sandwell and West Birmingham NHS Trust; University Hospitals Coventry and Warwickshire; The Shrewsbury and Telford Hospital NHS Trust; Oncology/Cancer Services; Haematology; Pathology; Medical and Dental; Healthcare Scientists; Gonzalez, M. Vega; Maybury, Bernard; James, Lisa; Chadderton, Nicola; Dowds, James; Rudzki, Zbigniew; Chaganti, SridharMYC/BCL6 DOUBLE HIT LYMPHOMA NEGATIVE FOR T(3;8) BCL6::MYC FUSION IS ASSOCIATED WITH INFERIOR SURVIVAL, IN CONTRAST WITH T(3;8) POSITIVE PSEUDO-DOUBLE HIT LYMPHOMA B Introduction: b A small proportion of large B cell non-Hodgkin lymphoma (NHL) has I MYC i and I BCL6 i rearrangements, detectable by fluorescence in-situ hybridisation (FISH) break-apart probes. Cases of I MYC/BCL2 i double-hit lymphoma without I BCL6 i rearrangement were excluded.Publication Aspirin as an adjuvant treatment for cancer : feasibility results from the Add-Aspirin randomised trial(Elsevier, 2019-08-30) Joharatnam-Hogan, Nalinie; Cafferty, Fay; Hubner, Richard; Swinson, Daniel; Sothi, Sharmila; Gupta, Kamalnayan; Falk, Stephen; Patel, Kinnari; Warner, Nicola; Kunene, Victoria; Rowley, Sam; Khabra, Komel; Underwood, Tim; Jankowski, Janusz; Bridgewater, John; Crossley, Anne; Henson, Verity; Berkman, Lindy; Gilbert, Duncan; Kynaston, Howard; Ring, Alistair; Cameron, David; Din, Farhat; Graham, Janet; Iveson, Timothy; Adams, Richard; Thomas, Anne; Wilson, Richard; Pramesh, C S; Langley, Ruth; University College London; The Christie Hospital; St James University Hospital; University Hospital Coventry and Warwickshire; Worcestershire Royal Hospital; Bristol Haematology & Oncology Centre; Churchill Hospital; Stoke Mandeville Hospital; Walsall Healthcare NHS Trust; University of Southampton; Morecambe Bay University Hospitals NHS Trust; National Institute for Health and Care Excellence; NCRI Consumer Liaison Group; Cardiff University; Royal Marsden Hospital; Cancer Research UK Edinburgh Centre; Western General Hospital; Beatson West of Scotland Cancer Centre; Southampton General Hospital; Velindre Cancer Centre; Leicester Royal Infirmary; University of Glasgow; Tata Memorial Hospital; Oncology/Cancer Services; Medical and Dental; Kunene, Victoria; Sothi, SharmilaBackground: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. Methods: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. Findings: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). Interpretation: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes.Publication Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial(Nature Publishing Group, 2023-07-07) Joharatnam-Hogan, Nalinie; Hatem, Duaa; Cafferty, Fay H; Petrucci, Giovanna; Cameron, David A; Ring, Alistair; Kynaston, Howard G; Gilbert, Duncan C; Wilson, Richard H; Hubner, Richard A; Swinson, Daniel E B; Cleary, Siobhan; Robbins, Alex; MacKenzie, Mairead; Sothi, Sharmila; Dawson, Lesley K; Capaldi, Lisa M; Churn, Mark; Cunningham, David; Khoo, Vincent; Armstrong, Anne C; Ainsworth, Nicola L; Horan, Gail; Wheatley, Duncan A; Mullen, Russell; Lofts, Fiona J; Walther, Axel; Herbertson, Rebecca A; Eaton, John D; O'Callaghan, Ann; Eichholz, Andrew; Kagzi, Mohammed M; Patterson, Daniel M; Narahari, Krishna; Bradbury, Jennifer; Stokes, Zuzana; Rizvi, Azhar J; Walker, Georgina A; Kunene, Victoria L; Srihari, Narayanan; Gentry-Maharaj, Aleksandra; Meade, Angela; Patrono, Carlo; Rocca, Bianca; Langley, Ruth E; Scott-Brown, Martin W G; MRC Clinical Trials Unit; Catholic University School of Medicine; The Institute of Cancer Research; The University of Edinburgh, Western General Hospital; The Royal Marsden NHS Foundation Trust; Cardiff University School of Medicine; University Hospitals Sussex NHS Foundation Trust; University of Glasgow; The Beatson West of Scotland Cancer Centre; The Christie NHS Foundation Trust; University of Manchester; Leeds Teaching Hospitals NHS Trust; Independent Cancer Patients; University Hospitals Coventry and Warwickshire NHS Trust; Western General Hospital; Worcestershire Acute Hospitals NHS Trust; The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust; Royal Cornwall Hospitals NHS Trust; Raigmore Hospital; St George's University Hospitals NHS Foundation Trust; University Hospitals Bristol and Weston NHS Foundation Trust; University Hospitals of Morecambe Bay NHS Foundation Trust; Portsmouth Hospitals University NHS Trust; Buckinghamshire Healthcare NHS Trust; South Tees Hospitals NHS Foundation Trust; West Suffolk Hospitals NHS Trust; University Hospital of Wales, Cardiff University; Salisbury NHS Foundation Trust; United Lincolnshire Hospitals NHS Trust; Milton Keynes University Hospital NHS Foundation Trust; Nottingham University Hospitals NHS Trust; Walsall Healthcare NHS Trust; University Hospitals Birmingham NHS Foundation Trust; Shrewsbury and Telford Hospital NHS Trust; MRC Clinical Trials Unit; Medical; Oncology/Cancer Services; Medical and Dental; Scott-Brown, Martin W G; Sothi, Sharmila; Victoria L KuneneBackground: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. Methods: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. Results: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. Conclusions: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.