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2. Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial

Author

Marks, David I, Kirkwood, Amy A, Rowntree, Clare J, Aguiar, Melanie, Bailey, Katharine E, Beaton, Brendan, Cahalin, Paul, Castleton, Anna Z, Clifton-Hadley, Laura, Copland, Mhairi, Goldstone, Anthony H, Kelly, Richard, Lawrie, Emma, Lee, SooWah, McMillan, Andrew K, McMullin, Mary Frances, Menne, Tobias F, Mitchell, Rachel J, Moorman, Anthony V, Patel, Bela, Patrick, Pip, Smith, Paul, Taussig, David, Yallop, Deborah, Alapi, Krisztina Zuborne, and Fielding, Adele K

Published
2022
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3. IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

Author

Mitchell, Rachel J., Kirkwood, Amy A., Barretta, Emilio, Clifton-Hadley, Laura, Lawrie, Emma, Lee, SooWah, Leongamornlert, Daniel, Marks, David I., McMillan, Andrew K., Menne, Tobias F., Papaemmanuil, Elli, Patel, Bela, Patrick, Pip, Rowntree, Clare J., Zareian, Nahid, Alapi, Krisztina Zuborne, Moorman, Anthony V., and Fielding, Adele K.

Published
2021
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5. Frames of Reference:Designing Cognitive Interventions to Improve Wayfinding for Cyclists

Author

Shepherd, Mia, Lawrie, Emma, Shealy, Tripp, Harrington, Deirdre, Maier, Anja Martina, Shepherd, Mia, Lawrie, Emma, Shealy, Tripp, Harrington, Deirdre, and Maier, Anja Martina

Abstract

Background: A benefit of academic conference is the ability for delegates to explore new locations in between conference sessions. During DCC’24 in Montreal, Canada, some delegates may explore the city’s historic landmarks and cultural sites. However, navigating vibrant streets and French colonial neighborhoods as visitors poses challenges, especially for those who decide to explore by bicycle. Current navigation systems, designed for continuous use, are impractical for cyclists because they pose safety hazards and slow down journeys which negatively impacts experiences. This study tested a human-cantered navigational approach aligned with working memory to improve wayfinding while cycling. It tested how providing directions using alternative frames of reference to current navigational systems, combined with environmental cues, influences cognitive memory. This study is related to design computing and cognition because it measured the effectiveness of redesigning and implementing a navigational system that considers human cognitive processes to enhance user experiences.

Published
2024

7. First Analysis of the UKALL14 Phase 3 Randomised Trial to Determine If the Addition of Rituximab to Standard Induction Chemotherapy Improves EFS in Adults with Precursor B-ALL (CRUK/09/006)

Author

Marks, David I, primary, Kirkwood, Amy A., primary, Rowntree, Clare J, primary, Aguiar, Melanie, primary, Bailey, Katharine E, primary, Beaton, Brendan, primary, Clifton-Hadley, Laura, primary, Lawrie, Emma, primary, Lee, SooWah, primary, McMillan, Andrew K, primary, Moorman, Anthony V., primary, Mitchell, Rachel J., primary, Patrick, Pip, primary, Menne, Tobias F, primary, Smith, Paul, primary, Wrench, Bela, primary, Alapi, Krisztina Zuborne, primary, and Fielding, Adele K., primary

Published
2019
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8. IKZF1alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

Author

Mitchell, Rachel J., Kirkwood, Amy A., Barretta, Emilio, Clifton-Hadley, Laura, Lawrie, Emma, Lee, SooWah, Leongamornlert, Daniel, Marks, David I., McMillan, Andrew K., Menne, Tobias F., Papaemmanuil, Elli, Patel, Bela, Patrick, Pip, Rowntree, Clare J., Zareian, Nahid, Alapi, Krisztina Zuborne, Moorman, Anthony V., and Fielding, Adele K.

Abstract

IKZF1deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+and BCR-ABL1−B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1−ΔIKZF1were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1(including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1and outcome is the older age of participants in our population. The impact of ΔIKZF1in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.govas #NCT01085617.

Published
2021
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9. Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations

Author

Gollins, Simon, primary, West, Nick, additional, Sebag-Montefiore, David, additional, Myint, Arthur Sun, additional, Saunders, Mark, additional, Susnerwala, Shabbir, additional, Quirke, Phil, additional, Essapen, Sharadah, additional, Samuel, Leslie, additional, Sizer, Bruce, additional, Worlding, Jane, additional, Southward, Katie, additional, Hemmings, Gemma, additional, Tinkler-Hundal, Emma, additional, Taylor, Morag, additional, Bottomley, Daniel, additional, Chambers, Philip, additional, Lawrie, Emma, additional, Lopes, Andre, additional, and Beare, Sandy, additional

Published
2017
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10. Fludarabine, Melphalan and Alemtuzumab Conditioned Reduced Intensity (RIC) Allogeneic Hematopoietic Cell Transplantation for Adults Aged >40 Years with De Novo Acute Lymphoblastic Leukemia: A Prospective Study from the UKALL14 Trial (ISRCTN 66541317)

Author

Okasha, Dina, primary, Kirkwood, Amy A, additional, Copland, Mhairi, additional, Lawrie, Emma, additional, McMillan, Andrew, additional, Menne, Tobias F., additional, Morley, Nick, additional, Rowntree, Clare, additional, Richardson, Deborah Susan, additional, Smith, Paul, additional, Fielding, Adele K., additional, and Marks, David, additional

Published
2015
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11. Pretreatment and postresection epidermal growth factor receptor (EGFR) pathway mutations in a prospective phase II trial (EXCITE) of preoperative cetuximab-containing chemoradiation (CRT) in locally advanced rectal cancer (LARC)

Author

Lawrie Emma, David Sebag-Montefiore, Shabbir Susnerwala, S. Myint, Sandy Beare, Mark Jitlal, Bruce Sizer, Philip Quirke, Nicholas P. West, Sharadah Essapen, Mark P Saunders, Simon Gollins, and Leslie Samuel

Subjects
Oncology, Surgical resection, Cancer Research, medicine.medical_specialty, biology, Cetuximab, Colorectal cancer, business.industry, Locally advanced, medicine.disease, Surgery, Internal medicine, medicine, biology.protein, Egfr signaling, Epidermal growth factor receptor, business, neoplasms, medicine.drug
Abstract

458 Background: Little data exists comparing pre- and post-CRT EGFR pathway mutations in LARC. Methods: Patients had MRI-defined LARC threatening or involving the surgical resection margin. CRT used pelvic radiotherapy (RT) 45Gy in 25 daily fractions with concurrent capecitabine (650mg/m2 bid PO 5 days/week), IV cetuximab (400mg/m2 one week prior then weekly at 250mg/m2 weeks 1-5) and IV irinotecan (weekly at 60mg/m2weeks 1-4). Surgery was 8 weeks after CRT. EGFR pathway mutations were not assessed prospectively. After study completion DNA was extracted from pre-treatment biopsies and post-resection specimens by macrodissecting areas of greatest tumour cell density. KRAS codons 12, 13, 61, 146, NRAS codons 12, 13, 61, PIK3CA codons 542, 545, 546, 1047 and the BRAF V600E hotspot were then pyrosequenced. Results: From 04/09-10/11, 80 patients commenced RT. 76 patients had surgery, with pathological complete response (CR) in 14 (18%) and near-complete (microfoci) in 6 (8%). Four patients had no surgery due to clinical CR. Pre-treatment mutation status was available in 78 patients with a KRAS codon mutation in 34 patients, BRAF in 3, NRAS in 3, PIK3CA in 10 and pathway (any mutation) in 45 (58%). Post-resection data in 54 patients showed 35 mutated codons in 32 patients (59%). 18 patients (33%) showed a discrepancy compared to pre-treatment biopsy. In 17 this was at a single codon, from wild-type (wt) to mutant (mut) in 9 (7x KRAS 12, 1x KRAS 13, 1x PIK3CA 542), from mut to mut in 1 (KRAS 12 c.35G>A to c.34G>T) and mut to wt in 7 (1x KRAS 12, 2x KRAS 13, 2x KRAS 146, 1x PIK3CA 542, 1x PIK3CA 545). One patient changed in 3 codons (mut to wt at KRAS 146 and PIK3CA 545 and wt to mut at KRAS 12). In 12 patients (22%) this changed overall EGFR pathway status (6x wt to mut and 6x mut to wt). Conclusions: Intratumour heterogeneity may explain the EGFR pathway codon changes causing sequencing from single areas of macrodissection to underestimate the tumour genomic landscape and presenting a challenge to personalised medicine. Cetuximab may also drive growth of undetectable mutant clones to detectable levels on pyrosequencing. Clinical trial information: 2007-006701-25.

Published
2014
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