Cancer Services

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Research outputs from Cancer Services at the RD&E.

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Now showing 1 - 5 of 25
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    Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services
    (Wiley, 2024-02-01) Drayson, M.; Jennis, T.; Laketic-Ljubojevic, I.; Patel, D.; Pratt, G.; Renwick, S.; Richter, A.; Wheeler, R.; Sheldon, J.; Sadler, R.; Stapleton, M.; Willis, F.; Whiston, M.
    Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.
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    Selection of patients with malignant melanoma for pelvic lymph node dissection (PLND) using CT-PET
    (Elsevier, 2023-12-01) Ali, T.; Powell, R.; Short, J.; Scatchard, K.; Stone, C.
    OBJECTIVES: In melanoma patients with positive pelvic nodes, pelvic lymph node dissection (PLND) to achieve fully resected disease status facilitates adjuvant-dose systemic therapy and avoids higher treatment doses with greater toxicity. This study aimed to test the accuracy of prediction of nodal involvement of the 2010 joint BAPRAS/BAD guidance compared with Positron Emission Tomography (CT-PET). METHODS: A retrospective review was undertaken of 26 melanoma patients undergoing PLND by a single surgeon between July 2012 and July 2020. The indications for performing PLND were in accordance with the 2010 guidance, but this was supplemented by CT-PET in 16/26 patients. RESULTS: Of the 26 patients undergoing PLND, 10 underwent surgery based upon the 2010 criteria alone and 16 underwent supplementary CT-PET. 17 patients had positive nodes on histology; of these, 13 had a positive CT-PET. Amongst node-negative patients, only one had a false positive CT-PET. CT-PET was 100% sensitive for pelvic nodal disease and 75% specific, with a positive predictive value for nodal involvement of 92%. Of the 10 patients who underwent PLND without CT-PET, only 4 had positive nodes while 6 patients had negative nodes. CONCLUSIONS: The 2010 guidelines remain broad and contributed to negative PLND in a third of our patients (9/26). Hence, the indications for performing PLND need to be revisited. Our series supports PET-CT as being 100% sensitive in the identification of pelvic nodal disease and 75% specific. We recommend that a positive PET-CT should be considered as the primary indication for PLND in melanoma patients.
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    Use of cytology fluid samples for predictive biomarker testing in lung cancer patients
    (Wiley, 2023-12-01) Hawkins, P.; Stevenson, T.; Powari, M.
    OBJECTIVE: To provide a method of directly using cytology fluid samples for predictive biomarker testing in lung cancer patients and to determine the efficacy of a variety of fluid sample types. METHOD: A review of our in-house data from a range of cytology samples including endobronchial ultrasound (EBUS) fine-needle aspirate (FNA) needle washings (NW) and serous effusions tested on the Biocartis Idylla platform. All fluid samples were originally tested using Sanger sequencing. RESULTS: Using our method for fluid samples all of our cytology samples tested for epithelial growth factor receptor (EGFR) yielded valid results on this platform and all variant cases identified. The data showed serous fluids provided the best quality DNA, and variant genotype reports were obtained within 150 minutes. CONCLUSION: Cytology fluid samples can be used for predictive biomarker testing for lung cancer patients to provide in-house results with all fluids providing good-quality DNA.
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    Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis
    (Nature, 2023-11-25) Fang, Z.; Corbizi Fattori, G.; McKerrell, T.; Boucher, R. H.; Jackson, A.; Fletcher, R. S.; Forte, D.; Martin, J. E.; Fox, S.; Roberts, J.; Glover, R.; Harris, E.; Bridges, H. R.; Grassi, L.; Rodriguez-Meira, A.; Mead, A. J.; Knapper, S.; Ewing, J.; Butt, N. M.; Jain, M.; Francis, S.; Clark, F. J.; Coppell, J.; McMullin, M. F.; Wadelin, F.; Narayanan, S.; Milojkovic, D.; Drummond, M. W.; Sekhar, M.; ElDaly, H.; Hirst, J.; Paramor, M.; Baxter, E. J.; Godfrey, A. L.; Harrison, C. N.; Méndez-Ferrer, S.
    Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2(V617F), CALR(ins5) or CALR(del52) peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.
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    Influence of family history on penetrance of hereditary cancers in a population setting
    (Elsevier, 2023-10-14) Jackson, L.; Weedon, M. N.; Green, H. D.; Mallabar-Rimmer, B.; Harrison, J. W.; Wood, A. R.; Ruth, K. S.; Tyrrell, J.; Wright, C. F.
    BACKGROUND: We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort. METHODS: We analysed 454,712 UK Biobank participants with exome sequence and clinical data (data collected between March 2006 and June 2021). We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome. We calculated survival to cancer diagnosis (controlled for sex, death, recruitment centre, screening and prophylactic surgery). FINDINGS: Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) than those without (13.0, 15.4 and 7.2). Penetrance to age 60 was also higher for carriers of a pathogenic MLH1 or MSH2 variant in those with a family history (30.9%, CI 18.1-49.3 and 38.3%, CI 21.5-61.8) versus those without (20.5% CI 9.6-40.5 and 8.3% CI 2.1-30.4), but not for MSH6 (6.5% CI 2.7-15.1 with family history versus 8.3%, CI 5.1-13.2). Relative risk increases were also observed both within and across conditions. INTERPRETATION: Individuals with pathogenic cancer syndrome variants may be at a less elevated risk of cancer in the absence of a first-degree family history, so in the context of results return, family history should be considered when counselling patients on the risks and benefits of potential follow-up care. FUNDING: The current work is supported by the MRC (grant no MR/T00200X/1). The MRC had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.