The Christie School of Oncology: Christie Research Publications Repository
Not a member yet
16373 research outputs found
Sort by
Circulating Tumor Cells Shed Shearosome Extracellular Vesicles in Capillary Bifurcations That Activate Endothelial and Immune Cells
No full textCirculating tumor cells (CTCs) and their clusters are the cellular drivers of metastasis. This study uses microfluidic models mimicking human capillary bifurcations to better understand how these cells interact with capillary beds. Patient CTCs, CTC-derived explant cells, and numerous cancer cell lines shed nuclei-free fragments in a cell size- and bifurcation-dependent manner. These shedding events, which reduces cell sizes up to 61%, facilitate CTC transit through bifurcations. The shed fragments are a novel subclass of large extracellular vesicles (LEVs) that we name 'shearosomes' based on their requirement of shear stress for their biogenesis, and whose proteome is associated with immune-related pathways. Shearosomes exhibit functions that are characteristic of previously identified extracellular vesicles (EVs), including cell-directed internalization by endothelial and immune cells, and intercellular communication capabilities such as disruption of endothelial barrier integrity, polarization of monocytes toward M2 tumor-promoting macrophages, and mediating interactions between endothelial and immune cells. These findings suggest that CTCs shed shearosomes within capillary beds that affect cells implicated in the metastatic cascade
Emotional strategies to enhance resilience in patients with cancer: a scoping review
No full textObjective: To map and summarize existing evidence on emotional strategies recommended for enhancing resilience in cancer patients, identify research gaps and inform future research. Methods: Following Joanna Briggs Institute (JBI) guidelines, a comprehensive search was conducted across 11 databases in English and Chinese, supplemented by citation tracking and manual searches for published and unpublished studies. Studies focusing on adult cancer patients and describing emotional strategies to enhance resilience were included and critically appraised using tools appropriate to its design. Data including qualitative descriptions of emotional strategies, quantitative resilience-related emotional variables, and emotional intervention details were extracted and analysed with NVivo 15. Results: A total of 33 papers were included, primarily from China (n = 16) and published as journal articles (n = 30) with randomized controlled trial designs (n = 14). Three key themes were identified: (a) emotion identification; (b) effective emotion regulation; and (c) emotional support from others. Emotional strategies were primarily implemented by nurses (n = 11), delivered online (n = 6) or face-to-face (n = 13). 'Positive' and 'emotions' were the most frequently mentioned words. Conclusions: Emotion identification, effective emotion regulation, and emotional support from others are essential for enhancing resilience in cancer patients. Many promising strategies remain underutilized and require further validation
Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: an international multicentre study
No full textBACKGROUND AND PURPOSE: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies. MATERIALS AND METHODS: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy. Agreement between healthcare professionals and people with lung cancer was quantified using Gwet's-AC(2) coefficient. The influence of clinical variables, comorbidities, and quality-of-life outcomes on agreement was examined through stratified analyses. RESULTS: We found varying levels of agreement between healthcare professionals and people with lung cancer. Bronchopulmonary haemorrhage and dysphagia exhibited very good agreement (meanAC(2) > 0.81), while cough and chest wall pain showed substantial agreement (meanAC(2) = 0.64 and 0.76, respectively). Dyspnoea had the lowest agreement (meanAC(2) = 0.59), with prior chemotherapy significantly reducing agreement levels. Chronic obstructive pulmonary disease (COPD) and early cancer stages also contributed to discrepancies in dyspnoea assessments. Regarding quality-of-life, the most relevant factor was fatigue, which reduced agreement in the assessment of dyspnoea (AC(2) = 0.55 vs 0.70), dysphagia (AC(2) = 0.48 vs 0.69), cough (AC(2) = 0.58 vs 0.82), and chest wall pain (AC(2) = 0.77 vs 0.91). CONCLUSIONS: Our findings indicate strong alignment between healthcare professionals' and people with lung cancer evaluations of observable treatment-related symptoms, but less consistency for subjective symptoms such as dyspnoea. Factors such as prior chemotherapy, COPD, and cancer stage should be considered when interpreting symptom assessments. Furthermore, our study underscores the importance of integrating quality-of-life considerations, particularly fatigue, into symptom evaluations to mitigate potential biases in symptom perception
Spatial Organisation of Tumour cDC1 States Correlates with Effector and Stem-Like CD8(+) T Cells Location
No full textCD8(+) T cells are central to targeting and eliminating cancer cells. Their function is critically supported by type 1 conventional dendritic cells (cDC1s), which both prime antigen-specific CD8(+) T cells in tumour-draining lymph nodes (tdLNs) and sustain primed CD8(+) T cells within tumours. Despite their importance, the spatiotemporal organisation of cDC1s within tumours and their diverse functional roles remain poorly understood. Here, we use scRNAseq and unbiased spatial analysis to construct a detailed map of cDC1 states and distribution within immunogenic mouse tumours during CD8(+) T-cell-mediated rejection. We reveal two distinct cDC1 activation states characterised by differential expression of genes linked to anti-tumour immunity, including Cxcl9 and Il12b. Strikingly, Il12b-expressing cDC1s are CCR7(+) and enriched at tumour borders, where they closely associate with stem-like TCF1(+) CD8(+) T cells. In contrast, CCR7(-) Cxcl9-expressing cDC1s are preferentially found within the tumour parenchyma alongside effector CD8(+) T cells. Analysis of a published dataset of human tumours similarly reveals a spatial association between CCR7(+) cDC1 and stem-like TCF1(+) CD8(+) T cells. These findings uncover a highly spatially coordinated interaction between cDC1s and CD8(+) T cells within tumours, shedding light on the intricate cellular dynamics that underpin effective anti-tumour immunity
Establishing priorities for clinical education research: exploring the views of UK professional and public stakeholders
No full textINTRODUCTION: High quality clinical education research is required to ensure optimal education and training of healthcare professionals. Such research should address stakeholder needs and have a clear route to achieving benefit. We conducted the first UK-wide priority setting exercise for clinical education research to identify research priorities and how they are determined. METHODS: We used a two-stage process, derived from similar studies, to identify the research priorities of stakeholders including funders, regulators, educators and public representatives. Stage one consisted of two rounds of online surveys, gathering free-text suggestions of priorities and rating the resulting statements. A public engagement author advised on wording. Stage two used a stakeholder workshop to discuss principles and processes for operationalising priorities and maximising impact. RESULTS: Round 1 survey respondents (n = 256) provided 1819 suggestions, from which content analysis synthesised 46 statements describing disparate research priorities. Distributions of ratings in Round 2 (n = 199) indicated that all were perceived as important by most respondents, although professionals and members of the public differed in their rating of some items. Workshop participants (n = 70) considered priorities to be dynamic and contextually dependent and linked to expected impact. DISCUSSION: The study identifies broad priorities for clinical education research, but recognises that simple prioritisation is insufficient, and develops understanding of how priorities arise, including differences between stakeholder groups, and changes over time. Recognising an integrated 'system of impact' may maximise opportunities for stakeholders-researchers, policy actors, knowledge users and funders-to effectively communicate and optimise research impact in the short and longer term
Considering late effects costs in radiotherapy funding
No full textRadiotherapy treatment can have transformative effects on a patient's overall health and wellbeing, yet current funding models are constrained to curative and palliative aspects of treatment delivery. This therapeutic focus, obscures wider costs associated with radiotherapy, both at a service level and for individual patients and their families. It is essential that policy and services consider quality of life after treatment, including identification and management of long-term side effects. Currently, a lack of service provision means that many patients have no access to services equipped to manage late toxicity or are utilising inappropriate services for their needs which could also be more costly for commissioners. As Integrated Care Boards (ICBs) take greater responsibility for the whole cancer pathway there are potential patient and cost benefits of rolling out more supportive oncology and late effects services. This should be supported with better data, including Patient Reported Data (PRD) and research on the level of need for broader aspects of radiotherapy and post treatment aspects of patient experience
619. ACUTE MYELOID LEUKEMIAS: DISEASE BURDEN AND MEASURABLE RESIDUAL DISEASE IN PROGNOSIS AND TREATMENT FLT3-ITD NGS-MRD refines risk stratification in NPM1 and FLT3 co-mutated AML beyond NPM1 PCR-MRD: Analysis of the UK NCRI AML17 and AML19 trials
No full textSafety and efficacy of combining midostaurin and gemtuzumab ozogamicin with induction chemotherapy in FLT3 mutated AML
No full textDespite the use of FLT3 inhibitors, outcomes for patients with FLT3 mutated (FLT3mut) AML remain suboptimal because of high rates of relapse. We evaluated the safety and efficacy of the combination of daunorubicin, cytarabine (DA), gemtuzumab ozogamicin (GO) and midostaurin (DAGO+m) for younger patients with newly diagnosed FLT3mut AML in the UK NCRI AML19 trial. 195 patients were randomised to receive DA with either one or two doses of GO (DAGO1 and DAGO2). 77 had a FLT3 mutation (60 had FLT3-ITD) and received midostaurin for two weeks after each chemotherapy course and then as maintainance for one year unless transplanted. 39 patients received midostaurin with DAGO1 (DAGO1+m) and 38 with DAGO2 (DAGO2+m). Their median age was 51y (range 20-74) and 16 (20%) were aged >60y. The overall response rate (CR + CRi) was 91%. Day 30 and day 60 mortality was 0% with no increase in toxicity compared to patients treated contemporaneously with DAGO1 and DAGO2 without midostaurin. 2y overall survival was 77%. 2y event-free survival and cumulative incidence of relapse were 62% and 31% respectively. MRD clearance was enhanced compared to patients with FLT3-mutated AML treated with DAGO1 and DAGO2 without midostaurin. 81% of evaluable patients were NPM1 MRD negative by RT-qPCR in the peripheral blood after course 2 (76% with DAGO1+m and 86% with DAGO2+m), 79% were MRD negative in the bone marrow by FLT3-ITD NGS, and all patients had FLT3-MRD levels below 0.01%. DAGO+m appears safe and effective . DAGO2+m will now be evaluated in a randomised study (OPTIMISE-FLT3, ISRCTN 34016918). Trial: ISRCTN78449203
Analysis of outcomes of patients with oligodendroglioma with focus on volumetric reduction
No full textBACKGROUND: This study aims to evaluate the surgical outcomes and prognostic factors influencing overall survival (OS) and progression-free survival (PFS) in patients with molecularly confirmed oligodendrogliomas focussing on the extent of resection (EOR) and volumetric analysis. METHODS: We conducted a retrospective analysis of 115 adult patients with oligodendroglioma at our institution from January 2010 to December 2020. Inclusion criteria encompassed histologically and molecularly confirmed grade 2 and 3 oligodendroglioma, age above 18 years, availability of pre- and postoperative imaging, and complete follow-up data. Surgical outcomes were categorized by EOR and volumetric assessments were performed using neuroimaging. Mean OS and PFS were calculated using the Kaplan-Meier method (As mortality was < 50%) and univariate/multivariate analyses were conducted to identify prognostic factors. RESULTS: The cohort had a median age of 42 years (range 18-77), with GTR achieved in 47% of primary operations. Median follow-up was 6.3 years. OS was significantly influenced by age (p < 0.0001) and EOR, with a mean OS of 134 months and a mean PFS of 117 months. Volumetric reduction of tumor volume greater than 80% correlated positively with both OS and PFS. The analysis also highlighted the importance of adjuvant therapy in improving PFS. CONCLUSION: This study confirms that younger age, extensive volumetric reduction, and intraoperative adjuncts are associated with improved OS and PFS in patients with oligodendroglioma. While the EOR impacts OS significantly in grade 3 tumors, further research is necessary to determine optimal surgical strategies for grade 2 oligodendrogliomas
Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers
No full textAdvanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic). Tumor androgen receptor signaling is associated with longer survival, whereas increased proliferation predicted shorter survival. In a pre-specified analysis, the previously identified decipher RNA signature was both prognostic and predicted survival benefit from docetaxel for metastatic cancers (biomarker-docetaxel interaction p = 0.039). Additionally, transcriptome-based classification of PTEN inactivation identified tumors more likely to have PTEN protein loss (p = 4 × 10(-37)) and metabolically perturbed metastatic cancers that had shorter survival with hormone therapies (p < 0.001) but exhibited docetaxel sensitivity (biomarker-docetaxel interaction p = 0.002). Transcriptome classifiers predict docetaxel benefit and could be clinically implemented for improved patient management