The Christie School of Oncology: Christie Research Publications Repository
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The economic burden of melanoma in the UK: a stage-specific cost analysis underscoring the importance of prevention and early diagnosis
No full textEsophageal toxicity after dose-escalated radiation therapy for stage II-III non-small cell lung cancer: a secondary analysis of the phase 2 randomized ARTFORCE PET-boost trial
No full textPURPOSE: We previously reported unexpected high rates of severe esophageal toxicity (ET) in patients with stage II-III non-small cell lung cancer treated in the randomized ARTFORCE PET-Boost dose-escalation trial (clinicaltrials.gov: NCT01024829). The aim of this study is to evaluate clinical factors and dose metrics associated with ET in patients treated within the trial. METHODS AND MATERIALS: Patients received 24 fractions of 3.0-5.4 Gy, planned isotoxically to the primary tumor as a whole (>4 cm) or to an (18)F-FDG-PET defined subvolume within the primary tumor. Lymph nodes received 24 × 2.75Gy. Radiation therapy was combined with concurrent or sequential chemotherapy, or given alone. We evaluated the incidence and time to grade ≥ 3 (G ≥ 3) ET, and patient-reported symptoms. Follow-up time was estimated using the reverse Kaplan-Meier method. Uni- and multivariable logistic regression analyses with Firth's penalization were performed to assess the associations between clinical variables, dose parameters, and the incidence of G ≥ 3 ET. RESULTS: Median follow-up was 73.3 months. Of 107 patients randomized, 24(22.4%) experienced G ≥ 3 ET. There were 3 (2.8%) ET-related deaths, all esophageal fistulas. Median esophagus mean dose and D0.1% (EQD2) were 25.2 Gy (IQR, 18.9-33.2), and 69.5Gy (IQR, 66.4-75.4), respectively. G ≥ 3 ET occurred less frequently (19/54[35.2%] vs 5/53[9.4%]; P = .001) after a dose constraint for esophagus + 5 mm was introduced mid-trial (D0.1% 50 Gy, near maximum doses, and the equivalent uniform dose, were significantly associated with G ≥ 3 ET in multivariable regression. CONCLUSIONS: Concurrent platinum-doublet chemotherapy, as well as high doses to the esophagus, was independently associated with risk of severe ET. Stricter dose constraints led to significant reduction in G ≥ 3 ET. Future dose-escalation studies should lower doses to the esophagus, especially when combined with concurrent chemotherapy
Borderline ovarian tumours
No full textKey content Borderline ovarian tumours (BOTs) are a diverse and heterogeneous set of diseases, which are encountered by all obstetricians and gynaecologists. They occur on average around 10 years earlier than malignant ovarian cancers and are associated with a significantly better prognosis. Preoperative diagnosis of BOTs is challenging as radiological features overlap with benign and malignant disease. There are no blood tumour markers that can delineate between benign, malignant and BOTs. Oncological safety should be maintained in surgical management. Fertility-sparing management is acceptable but should include full surgical staging. There is no role for adjuvant treatment in the management of BOTs. Recurrence rates vary between 2 and 24% and invasive recurrence rates are low. Recurrences can occur late; therefore, follow-up is recommended beyond 5 years of initial diagnosis.Learning objectives To gain knowledge of the epidemiology, pathology, and biology of BOTs. To understand the radiological challenges associated with BOTs and the effect this has on planning surgical management. To understand the principles of surgical management, including fertility-sparing surgery and the importance of a personalised approach. To appreciate the role of surveillance for BOTs including the role of ultrasound scans and tumour markers
Provision of medical same day emergency care services within the UK: analysis from the Society for Acute Medicine Benchmarking Audit
No full textAIM: To evaluate the current provision of medical same day emergency care (SDEC) services within the UK, and the current utilisation of these pathways in the assessment of unplanned medical attendances. DESIGN: Survey data was used from the Society for Acute Medicine Benchmarking Audit (SAMBA), including anonymised patient-level data collected annually using a day of care survey. SETTING: Hospitals accepting unplanned medical attendances within the UK, 2019-2023. PARTICIPANTS: 34 948 unplanned and 4342 planned attendances across 188 hospital sites. RESULTS: 29.8% of unplanned medical attendances received their initial medical assessment within SDEC services (2403 patients in SAMBA23), with the proportion increasing over time. 82.4% of patients assessed in SDEC services were discharged without overnight admission. Assessment in SDEC services was less likely in male patients, patients with frailty and older adults (all p<0.005).Selected operational standards for SDEC delivery, set by the Society for Acute Medicine, were met in 64%-91% of hospitals. Most hospitals (82%) accepted referrals from emergency department triage and 63% accepted referrals directly from the paramedic team. 38% of hospitals did not use a recognised selection criteria to identify suitable patients for SDEC and only 8% used a criteria designed to identify patients suitable for discharge. Overall, 34.7% of medical attendances discharged without overnight admission received their medical assessment in locations other than SDEC. CONCLUSIONS: Medical SDEC provides assessment for one-third of patients seen through acute medicine services. Although the proportion of patients assessed within SDEC is increasing, further innovation and improvements are needed to ensure appropriate patients access this service
A national framework for moving towards more environmentally sustainable radiotherapy: the green radiotherapy framework
No full textBACKGROUND: Healthcare currently contributes 4-5 % of global greenhouse gas emissions worldwide, adding to the climate crisis which threatens global health and wellbeing as well as the delivery of healthcare. Oncology patients may be particularly vulnerable to these threats. The emerging principles of environmentally sustainable healthcare, and our nascent understanding of the environmental impact of radiotherapy has begun to suggest ways in which carbon emissions associated with this treatment can be reduced, whilst quality is maintained. METHODS: A review of relevant literature, along with a survey of UK departments, was used to assess actions that can be taken to reduce the climate impact of radiotherapy. RESULTS: The 'Green Radiotherapy' Framework draws on this evidence to systematize actions departments can take to reduce their environmental impact. CONCLUSION: We encourage radiotherapy departments to use the Framework to work towards a shared goal: sustainable cancer care for a future in which we and our patients can all thrive
UK real-world data of radium-223 dichloride in metastatic prostate cancer
No full textOBJECTIVES: To evaluate the treatment patterns and outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride in the UK. METHODS: Patients initiating treatment with radium-223 from 1 September 2017 to 1 September 2019 in 15 UK oncology centres were included. Demographics, treatment, clinical, biochemical, and outcome data were collected prospectively. Quality of life data were obtained using analgesic scores and components of the Functional Assessment Cancer Therapy - Prostate (FACT-P) questionnaire. RESULTS: A total of 550 consecutive, evaluable patients were included. The most common prior therapy for mCRPC was enzalutamide. At final analysis, after a median follow-up of 13.3 months, 55% of patients had completed six cycles of treatment. Median overall survival was 13.7 months (95% confidence interval, 12.6-14.8 months). Poor performance status, prior use of docetaxel in the metastatic hormone sensitive prostate cancer (mHSPC) setting, number of lines of prior treatment, and abnormal platelet count were independent variables associated with poor prognosis. Adverse events led to treatment discontinuation in 5.5% of patients. WHO analgesic scores and FACT-P questionnaire scores did not significantly change after treatment administration. CONCLUSION: The National Radium-223 Dichloride Audit was the first and largest multicentre prospective analysis of treatment patterns, outcomes, and quality of life data in patients treated with radium-223 in the UK. Radium-223 can be administered safely to patients previously treated with other life-prolonging therapies. Efficacy and safety data compare favourably with clinical trial and other real-world data. Our results suggest that its use earlier in the treatment pathway is associated with longer survival
DICER1-related pediatric thyroid neoplasm with follicular and morular growth: a tumor that did not read the textbook
No full textThyroid lesions associated with DICER1 syndrome include multifocal hyperplastic and benign neoplastic proliferations (follicular nodular disease) with characteristic macrofollicular and/or intrafollicular centripetal papillary growth patterns, frequently associated with atrophic and involutional changes. There are also well-differentiated thyroid carcinomas showing intermediate-type nuclei, sometimes combining high-grade areas (tumor-in-tumor pattern) and poorly differentiated carcinomas. Here, for the first time, we describe an encapsulated follicular cell thyroid tumor showing a mixed follicular and morular growth pattern, which presented in an 11-year-old girl with follicular nodular disease and a constitutional (germline) DICER1 p.(Tyr1357fs*18) pathogenic variant. The tumoral follicular component showed colloid and tumor cells with round nuclei, frequent chromatin clearing, and overlapping without grooves or pseudoinclusions (intermediate-type nuclei). There were scattered mitotic figures, but no tumor necrosis, infiltration, or vascular invasion. The morular structures lacked keratinization. The follicular areas were positive for TTF1/NKX2, PAX8, thyroglobulin, thyroperoxidase, keratin clones CKAE1/AE3 and 34bE12, CK19, and vimentin, whereas the morular component was positive for CKAE1/AE3, CK19, CD10, and CDX2. Aberrant (nuclear and cytoplasmic) immunolabeling pattern for β-catenin was limited to the morular structures. The Ki67 proliferation index was 21% in the follicular component and less than 1% in the morulae. In addition to the constitutional DICER1 p.(Tyr1357fs*18) variant, the somatic DICER1 p.(Asp1910Tyr) oncogenic variant and the somatic CTNNB1 p.(Thr41Ala) oncogenic variant were also identified in this tumor. This 'DICER1-related pediatric thyroid neoplasm with follicular and morular growth' expands the spectrum of DICER1-associated thyroid lesions. Indirectly, the absence of follicular markers only in the areas with WNT/β-catenin pathway activation (morular structures) in this neoplasm could explain the absence of follicular differentiation in cribriform morular thyroid carcinoma. The additional study of one of the accompanying thyroid nodules (follicular nodular disease) confirmed the constitutional DICER1 variant, along with DICER1 p.(Asp1709Gly) and p.(Asp1810Val) variants
RADAR: an international trial comparing ABVD with brentuximab vedotin plus AVD in limited-stage hodgkin lymphoma
No full textDose mapping using image registration for reirradiation: a systematic review
No full textBACKGROUND: As reirradiation becomes increasingly common due to longer patient survival, accurately mapping previous radiation dose is essential to balance toxicity and tumour control. Image registration (IR) is widely used to align previous dose distributions with current anatomy. However, significant anatomical changes between treatment courses pose unique challenges, and it remains unclear how existing IR practices-largely developed for other contexts-translate to reirradiation. This systematic review aims to report on what is currently being done in the field regarding the use of IR for dose mapping in reirradiation scenarios, identify methodological gaps, and propose recommendations to improve reproducibility and clinical utility. METHODS: We performed a PRISMA-compliant search for full-length articles (PubMed and Scopus) and conference abstracts (ScienceDirect and AAPM) that explicitly referenced IR for dose mapping in reirradiation. Each article was reviewed by at least two independent reviewers, with key data extracted on IR approaches and evaluation strategies. RESULTS: As of mid-May 2025, 34 articles and 30 abstracts were selected. Most studies lacked comprehensive evaluation: about one-third reported geometric accuracy metrics, and few included dosimetric assessments or uncertainty estimation. Multimodal reirradiation, non-external beam techniques, and paediatric populations were notably underrepresented. CONCLUSION: Based on the synthesis of current literature and expert consensus, we propose three clinical and ten research recommendations to support reproducible research and clinical practices. Clear and consistent reporting of registration methods, geometrical and dosimetrical assessments are essential to improve the reliability of dose mapping and to support safer, evidence-based use of image registration in the reirradiation setting