The Christie School of Oncology: Christie Research Publications Repository
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Anaesthesia for paediatric radiotherapy: A narrative review
No full textINTRODUCTION: Radiotherapy is currently used in approximately one-third of children with cancer. Treatments are typically received as weekday outpatient appointments over 3-6 weeks. The treatment is painless but requires a still, co-operative patient who can lie alone in set positions, facilitated by the use of immobilisation devices, for up to 1 h. METHODS: We conducted a literature search to identify relevant articles relating to radiotherapy treatment. Key search terms included: 'radiotherapy'; 'proton beam'; 'photon'; 'sedation'; 'anaesthesia'; and 'paediatric'. The abstracts of identified articles were assessed for relevance and their references reviewed for further relevant publications. RESULTS: The requirement for anaesthesia is almost exclusively limited to younger children, who are committed to daily anaesthetics over the duration of their treatment course. Centres tend to adopt a primary anaesthetic technique of either general anaesthesia using a supraglottic airway device or deep sedation, with spontaneous ventilation maintained. A full variety of anaesthetic drugs has been used with insufficient evidence to support a standardised primary approach but an apparent global trend towards propofol by infusion for sedation. Children may become acutely unwell during their treatment course and systems for escalation of clinical care in this event are vital. Distance from the patient for staff radiation shielding, patient positioning for treatment delivery and the use of immobilisation devices may provide additional access challenges in the event of an emergency. DISCUSSION: The requirement for anaesthesia for paediatric radiotherapy is typically confined to younger children. Patients may be unwell, with several specific considerations related to their cancer diagnosis and the impact of various treatments including surgery and chemotherapy, in addition to the radiotherapy. A multidisciplinary team approach to all aspects of care is imperative in this group of high-risk patients
Exploring gene expression in localised prostate cancer: insights from a randomised control trial with a focus on hypoxia and angiogenic genomic biomarkers post-EBRT and HDR-BTb
No full textAn assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma
No full textBackground: Treatment of Ewing sarcoma is associated with severe toxicities including chemotherapy-induced mucositis. Here we investigated the role of circulating biomarkers and genetic factors in predicting mucositis severity in Ewing sarcoma. Methods: Blood samples were collected from 111 Ewing sarcoma patients during treatment. Circulating total CK18 and FLT3 ligand concentrations were measured in plasma. Germline DNA was used to investigate associations between genetic variants and mucositis severity. Results: An increase in median tCK18 levels was observed during cycle 1, from 189 (86-736) U/L at cycle 1 day 1 pre-chemotherapy to 311 (141-1138) U/L on cycle 1 day 2-5 (p = 0.0001). Patients experiencing a >= 1.3-fold increase in tCK18 at 48-120 hours after administration of the first cycle had a higher likelihood of developing grade 3 mucositis in any cycle (p = 0.044). Genetic analysis revealed an association between a gene set associated with chemotherapy induced severe mucositis and differentially expressed genes set for minor salivary gland (p = 4.12 x10-4) and esophageal mucosa (p = 1.55 x10-5). Discussion: Early increases in circulating CK18 levels correlated with grade 3 mucositis. Genome-wide association analysis highlighted genes that may be associated with mucositis pathology, offering insights into biological mechanisms underlying susceptibility
Tolerability and clinical activity of novel first-in-class oral agent, inobrodib (CCS1477) with pom-dex in RRMM
No full textErratum to: tracking and reducing SF(6) usage in radiation oncology: a step toward net-zero health care emissions
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Life after pelvic exenteration for rectal cancer: the patient and carer perspective on long term consequences and survivorship
No full textOBJECTIVE: To explore the perspectives and experiences of patients and carers living with the long-term consequences of pelvic exenteration. SUMMARY BACKGROUND DATA: Pelvic exenteration is accepted as the standard of care for selected patients with locally advanced or recurrent rectal cancer. With contemporary 5-year survival reported at 40-60%, the number of long-term survivors is expected to increase. The long-term consequences of such radical surgery for patients and their survivorship needs are not well understood. METHODS: This was an exploratory, qualitative study conducted at a high-volume pelvic exenteration centre. Semi-structured interviews were conducted with survivors of pelvic exenteration surgery for locally advanced or recurrent rectal cancer and their carers. Purposive sampling was used to ensure a diverse cohort. Data were thematically analysed. RESULTS: Three major themes were identified: 1. The consequences of surgery are the price you pay for survival: the majority of participants accepted the sequelae of surgery as the cost of survival. 2. Our lives are changed forever: Adjusting to changes in body appearance and function was an ongoing challenge. Chronic pain, stomas, altered bowel function and mobility issues impacted work and social life. 3. The good days and bad days as a survivor: While several participants reported a more positive approach to life, many were living with a pervasive fear of recurrence and/or dying, and the ripple effect on family and friends was significant. CONCLUSIONS: Although survivors of pelvic exenteration accept the long-term consequences of surgery as the price of survival, these are significant, and improved access to support services in the community may better equip survivors to manage these challenges
Development of the SCNS-TARGET: a new tool to assess unmet needs in cancer patients utilising immuno-, biological or precision therapies
No full textPURPOSE: Develop an instrument to assess unmet needs in cancer patients using immuno-, biological and precision (IBP) therapies. METHODS: Development followed COSMIN guidance. Instruments to assess unmet needs of advanced cancer patients were identified, and quality and content were evaluated in a systematic review (Phase 1). Semi-structured interviews with patients utilising IBP therapies (n = 31) and healthcare professionals (n = 22) explored supportive care needs (Phase 2). Phase 3 selected a base instrument to adapt, generated new items and iteratively refined these through six meetings involving professionals (n = 8) and public and patient involvement representatives (n = 9) and patient cognitive interviews (n = 16). Phase 4 piloted the new instrument (n = 50 patients). RESULTS: Twenty-four instruments were identified; none was developed for patients utilising IBP therapies (Phase 1). Ten domains of unmet needs were identified from the interview data (Phase 2). SCNS-SF34 was selected as the base instrument. Informed by interview data, an 'add-on module' (SCNS-TARGET) was developed for patients utilising IBP therapies comprising 25 questions (psychological domain, 7 items; information, 6; healthcare, 5; economic, 3; role, 2; physical, 1; social, 1; Phase 3). Levels of missingness were low; reliability varied across questions, and, on average, patients reported 7.40 (standard deviation = 8.43) unmet needs on SCNS-TARGET (Phase 4). CONCLUSIONS: SCNS-TARGET is designed for use alongside SCNS-SF34 to assess unmet needs in those using IBP therapies. Content and face validity have been established. IMPLICATIONS FOR CANCER SURVIVORS: SCNS-TARGET can help researchers and healthcare professionals determine unmet needs and inform requirements for new services and interventions, among patients using IBP therapies
A survey of dosimetry quality assurance practice at UK small animal radiation research platform (SARRP) facilities
No full textIntroduction: Improvements in preclinical radiation research have been made to better mimic the equipment and techniques implemented in the clinic. The development of dedicated small animal radiation units facilitates such advances by combining treatment planning, image guidance and conformal delivery. One area significantly behind its clinical equivalent are standardised dosimetry quality assurance (QA) protocols, hampering the translatability of results into the development of clinical interventions.Approach: The aim of the study described herein was to summarise the current QA procedures implemented at several institutions on Small Animal Radiation Research Platforms (SARRPs), the system used by the six institutions surveyed, and to determine the barriers to implementing a standard dosimetry protocol. Participants at UK research institutions were invited to complete a questionnaire to ascertain their current preclinical QA practice.Main results: All participants involved undertake regular dose output measurements and most perform image guidance QA measurements. Consistency in QA procedures differed when more complex plan verification or end-to-end testing was discussed.Significance: This survey demonstrates that, although improvements are being made in the awareness of the importance of regular dosimetry tests, there is still a way to go to standardise the procedures with regards to more complex verifications. Incorporating robust QA procedures and strict dose constraints would ensure the reliability and ethical integrity of experiments involving small animals. This approach not only protects the welfare of the animals but also enhances the quality and reproducibility of the preclinical results
Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: results of the EORTC 1333/PEACE-3 trial
No full textBACKGROUND: The EORTC 1333 'PEACE-3' study investigated the combination of enzalutamide and 6 monthly injections of radium-223 (Ra223) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. MATERIALS AND METHODS: From November 2015 to March 2023, 446 patients, including 11 who received abiraterone, were randomized to enzalutamide (without placebo) or enzalutamide combined with six cycles of Ra223. As of March 2018, the co-administration of zoledronic acid or denosumab was mandatory. The primary endpoint was radiological progression-free survival (rPFS) by investigator assessment. Key secondary endpoints included overall survival (OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event. RESULTS: The hazard ratio (HR) for rPFS was 0.69 [95% confidence interval (CI) 0.54-0.87, P = 0.0009], with a median rPFS of 16.4 months (95% CI 13.8-19.2 months) in the enzalutamide arm and 19.4 months (95% CI 17.1-25.3 months) in the combination arm. At the preplanned interim analysis conducted at 80% of the OS events, the HR for OS was 0.69 (95% CI 0.52-0.90, P = 0.0031), with a median OS of 35.0 months (95% CI 28.8-38.9 months) in the enzalutamide arm and 42.3 months (95% CI 36.8-49.1 months) in the combination arm. Due to non-proportional hazards, this will be tested further at the final OS analysis. Treatment-emergent adverse events (TEAEs) ≥ grade 3 were recorded in 55.8% and 65.6% of the patients in the enzalutamide and combination arms, respectively. The most frequent grade ≥3 TEAEs in the combination arm were hypertension (34%), fatigue (6%), fracture (5%), anemia (5%), and neutropenia (5%). Fractures [either treatment-emergent or post-treatment, symptomatic or pathologic, or with or without bone-protecting agent (BPA) use] were reported in 30 (13.4%) patients in the enzalutamide arm and 53 patients (24.3%) in the combination arm. CONCLUSION: PEACE-3 demonstrates that combining enzalutamide with Ra223 as first-line therapy for mCRPC significantly improves rPFS. Although statistically significant at the OS interim boundary, the study will continue to the final OS analysis