The Christie School of Oncology: Christie Research Publications Repository
Not a member yet
16373 research outputs found
Sort by
The landscape of N(6)-methyladenosine in localized primary prostate cancer
No full textN(6)-methyladenosine (m(6)A), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the m(6)A landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. m(6)A abundance varied dramatically across tumors, with global patterns emerging via complex germline-somatic cooperative regulation. Individual germline polymorphisms regulated m(6)A abundance, cooperating with somatic mutation of cancer driver genes and m(6)A regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific m(6)A patterns. Tumor hypoxia dysregulates m(6)A profiles, bridging prior genomic and proteomic observations. Specific m(6)A sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. m(6)A dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis
A plain language summary of atezolizumab compared with single-agent chemotherapy in participants with non-small cell lung cancer who should not receive platinum-based chemotherapy (the IPSOS study)
No full textDurable responses in patients with large B-cell lymphoma and 3+prior lines of therapy who either paused or discontinued epcoritamab monotherapy while in complete response
No full textPolydopamine nanocomposite hydrogel for drug slow-release in bone defect repair: a review of research advances
No full textIn recent years, hydrogels have emerged as promising candidates for bone defect repair due to their excellent biocompatibility, high porosity, and water-retentive properties. However, conventional hydrogels face significant challenges in clinical translation, including brittleness, low mechanical strength, and poorly controlled drug degradation rates. To address these limitations, as a multifunctional polymer, polydopamine (PDA) has shown great potential in both bone regeneration and drug delivery systems. Its robust adhesive properties, biocompatibility, and responsiveness to photothermal stimulation make it an ideal candidate for enhancing hydrogel performance. Integrating PDA into conventional hydrogels not only improves their mechanical properties but also creates an environment conducive to cell adhesion, proliferation, and differentiation, thereby promoting bone defect repair. Moreover, PDA facilitates controlled drug release, offering a promising approach to optimizing treatment outcomes. This paper first explores the mechanisms through which PDA promotes bone regeneration, laying the foundation for its clinical translation. Additionally, it discusses the application of PDA-based nanocomposite hydrogels as advanced drug delivery systems for bone defect repair, providing valuable insights for both research and clinical translation
Electrochemotherapy for cutaneous kaposi sarcoma: a European register-based cohort study from the international network for sharing practices of electrochemotherapy (InspECT) (vol 51, 110099, 2025)
No full textClinical characteristics, healthcare resource use, and survival outcomes among patients with advanced NSCLC tested for KRAS mutations in France, the United Kingdom, and Switzerland
No full textOBJECTIVE: To evaluate real-world patient characteristics, healthcare resource use (HRU), and clinical outcomes among patients with advanced or metastatic (A/M) non-small cell lung cancer (NSCLC) stratified by KRAS mutation status (KRAS G12C, KRAS non-G12C, and KRAS wild-type[WT]). METHODS: This retrospective chart review included adults with A/M NSCLC and known KRAS status who received second- or third-line non-targeted therapy (index therapy) in France, the UK, or Switzerland. Patient characteristics, HRU, and key clinical outcomes-including time to treatment discontinuation (TTD), progression-free survival (PFS), and overall survival (OS)-were analyzed using the Kaplan-Meier method and log-rank methods. Exploratory multivariate Cox models adjusted for clinical covariates. RESULTS: The study included 211 patients (France: 192, UK: 13, Switzerland: 6), with 53.1% having KRAS G12C, 21.8% KRAS non-G12C, and 25.1% KRAS WT NSCLC. Median age was 66 years; 62.1% were male, and 95.8% were current/former smokers. Baseline characteristics were comparable across KRAS subgroups. HRU was high, including 125 unplanned healthcare provider visits, primarily to general practitioners (42.4%) and specialists (24.0%). Hospitalization was frequent (70.1% of patients), with 40.8% experiencing unplanned admissions, largely due to disease complications (54.2%) and grade 3/4 adverse events (24.4%). Median TTD, PFS, and OS were comparable across KRAS subgroups for second-line (4.4-4.7 months, 5.3-6.3 months, and 11.2-15.0 months) and third-line (3.2-4.1 months, 3.4-5.2 months, and 5.1-9.2 months) therapy. Multivariate analysis showed that KRAS status, performance status, histology, and comorbidities were not significantly associated with survival outcomes. CONCLUSIONS: Patients with advanced NSCLC, regardless of KRAS mutation status, experience a substantial disease burden, frequent hospitalizations, and poor clinical outcomes. These findings highlight the urgent need for more effective treatment options for advanced NSCLC, including therapies tailored to KRAS-mutated disease
The design and initial service evaluation of a virtual tour of a radiotherapy department to improve patient experience
No full textIntroduction: For any patient's cancer journey, effective communication and helpful information are key to staying informed and reducing anxiety; for radiotherapy, ideally before treatment commencement. This paper details the initial design and service evaluation of a virtual tour (VT) aimed at familiarising patients with the department before treatment starts.Methods: Created by local digital science students, with input from hospital Patient Public Involvement groups, patients were recruited (after their initial planning visit) into non-VT and VT groups; the latter viewing the VT before their first treatment. Both groups completed identical online surveys with Likert-style questions and free-text entry to assess knowledge and understanding.Results: Twenty-three completed survey responses were received: 9 and 14 from the non-VT and VT groups, respectively. 66.7% of the non-VT group felt anxious attending the department for the first time; compared with 28.6% in the VT group. Key comments included 'not now that I've seen the video' 92.9% of the VT group understood the queue calling and changing room systems compared with 55.6% in the non-VT group. 85.7% of the VT group knew what to expect in the treatment room, compared to 33.3% in the non-VT group. Key comments included 'the video helped'. Other comments included 'excellent idea' and 'alleviates the concerns about where to go and what to expect ahead of that first visit'.Results: Twenty-three completed survey responses were received: 9 and 14 from the non-VT and VT groups, respectively. 66.7% of the non-VT group felt anxious attending the department for the first time; compared with 28.6% in the VT group. Key comments included 'not now that I've seen the video' 92.9% of the VT group understood the queue calling and changing room systems compared with 55.6% in the non-VT group. 85.7% of the VT group knew what to expect in the treatment room, compared to 33.3% in the non-VT group. Key comments included 'the video helped'. Other comments included 'excellent idea' and 'alleviates the concerns about where to go and what to expect ahead of that first visit'.Conclusion: The implementation of the VT has proved beneficial to patients, providing key information prior to treatment start, alleviating concerns and resulting in improved patient experience without the need for an extra visit
Challenges of small cell lung cancer heterogeneity and phenotypic plasticity
No full textSmall cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with ~7% 5-year overall survival reflecting early metastasis and rapid acquired chemoresistance. Immunotherapy briefly extends overall survival in ~15% cases, yet predictive biomarkers are lacking. Targeted therapies are beginning to show promise, with a recently approved delta-like ligand 3 (DLL3)-targeted therapy impacting the treatment landscape. The increased availability of patient-faithful models, accumulating human tumour biobanks and numerous comprehensive molecular profiling studies have collectively facilitated the mapping and understanding of substantial intertumoural and intratumoural heterogeneity. Beyond the almost ubiquitous loss of wild-type p53 and RB1, SCLC is characterized by heterogeneously mis-regulated expression of MYC family members, yes-associated protein 1 (YAP1), NOTCH pathway signalling, anti-apoptotic BCL2 and epigenetic regulators. Molecular subtypes are based on the neurogenic transcription factors achaete-scute homologue 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), the rarer non-neuroendocrine transcription factor POU class 2 homeobox 3 (POU2F3), and immune- and inflammation-related signatures. Furthermore, SCLC shows phenotypic plasticity, including neuroendocrine-to-non-neuroendocrine transition driven by NOTCH signalling, which is associated with disease progression, chemoresistance and immune modulation and, in mouse models, with metastasis. Although these features pose substantial challenges, understanding the molecular vulnerabilities of transcription factor subtypes, the functional relevance of plasticity and cell cooperation offer opportunities for personalized therapies informed by liquid and tissue biomarkers
Definition of resectable stage III non-small cell lung cancer: a systematic review from EORTC lung cancer group
No full textBACKGROUND: Stage III non-small cell lung cancer (NSCLC) is a heterogenous disease requiring a multimodality treatment approach. For resectable stage III NSCLC, treatments incorporating surgery might be beneficial, however, a definition on resectable disease is lacking. The European Organization for the Treatment and Research of Cancer (EORTC) Lung Cancer Group initiative aims to provide a uniform definition of resectable stage III NSCLC. As part of this initiative, we conducted a systematic review to identify definitions on resectability; the medical specialties involved for making the decision and the required work-up aiding the decision. METHODOLOGY: Studies were included if they provided data or definitions on resectability in stage III NSCLC and were published in English, Dutch, or French between 2005- 2022. RESULTS: Out of 70 eligible articles, 46 provided tumour characteristics determining resectability. Factors against resection included: N3 or bulky N2 disease and locally invasive tumours. Factors favouring resection included N2-single station involvement and cT3N1. It remained unclear whether N2-multiple station and cT4N0-1 without invasion were defined as resectable. A multidisciplinary board including a thoracic surgeon, a medical (pneumo)oncologist and a radiation oncologist were involved in the decision in 95% of studies. PET-CT was considered standard in 70% and brain MRI/CT in 89% of the studies. A pathological mediastinal nodal confirmation was mandatory in 80% of the studies. CONCLUSIONS: This systematic literature review highlights tumour characteristics related to resectability, the specialties responsible for the decision and the most appropriate staging work-up in stage III NSCLC
