The Christie School of Oncology: Christie Research Publications Repository
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Radiotherapy outcomes in patients with interstitial lung disease and interstitial lung abnormalities: adverse events and survival from a UK tertiary centre
No full textBackground: Interstitial lung disease (ILD) encompasses a spectrum of inflammatory and fibrotic lung conditions. Interstitial lung abnormalities (ILA) are incidental radiological findings with the potential to progress to clinical ILD. Evidence guiding radiotherapy in patients with ILD and ILA is very limited. Methods: This retrospective cohort study included patients receiving curative-intent radiotherapy with or without chemotherapy at a UK tertiary oncology centre over a seven-year period. Patients with a prior ILD diagnosis or computer tomography (CT) features suggestive of ILA were identified and reviewed by specialist ILD radiologists. Patients were classified into 3 groups: ILD, ILA, or no radiological evidence of ILD/ILA. Clinical outcomes and adverse events were analysed. Results: Of 1693 patients referred for radiotherapy, 163 underwent specialist radiological review: 53 ILD, 53 ILA, and 57 with no ILD/ILA features. Survival outcomes differed significantly between groups. Median overall survival (OS) was 9.4 months (ILD), 14.7 months (ILA), and 22.5 months (no ILD/ILA) (p = 0.001). On multivariable analysis, ILD was independently associated with worse OS (HR 2.88). Grade 5 pneumonitis occurred in 13 % of ILD patients, 6 % with ILA, and 0 % with no ILD/ILA features. Conventional radiotherapy was associated with higher treatment-related adverse events compared to hypofractionated regimens. Conclusions: Patients with ILD experience significantly worse survival and higher risk of adverse events, including fatal pneumonitis, following radiotherapy. ILA represents an intermediate-risk group. These findings highlight the need for improved pre-treatment identification and risk stratification using radiological and clinical tools, and highlights the importance of prospective validation in future studies
Survivin recombinant overlapping peptide (ROP) vaccine in advanced solid tumours: a first-in-human, multicentre, open-label, phase 1a dose-escalation study
No full textBackground Survivin, an inhibitor of apoptosis protein (IAP), is highly expressed in various cancers but has weak immunogenicity as a self-derived tumour-associated antigen (TAA). OVM-200, a survivin recombinant overlapping peptide (ROP) vaccine, consists of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, preserving T-cell and most antibody epitopes. OVM-200 elicits both cellular and humoral immune responses against survivin-expressing cancer cells. This phase 1a, multicentre, open-label trial (OVM-200-100) evaluates OVM-200 as a therapeutic vaccine in patients with non-small cell lung, ovarian, and prostate cancer. This Phase 1 trial is also the first time the ROP technology platform has been used in human trials. Methods Twelve eligible patients received three subcutaneous OVM-200 doses at 2-week intervals using a 3 + 3 dose-escalation design. Four dose levels (250, 500, 1000, and 2000 mu g) were tested to determine the optimal dose for phase 1b. The primary endpoint was safety and tolerability, while secondary endpoints included immunogenicity (antibody and T-cell response) and tumour response (RECIST criteria). This trial was registered with ClinicalTrials.gov (NCT05104515) and EudraCT (2021-001545-12) and took place from 28/09/2021 to 04/05/2023. Findings OVM-200 was well tolerated, with no serious adverse drug reactions (ADRs) or dose-limiting toxicities (DLTs). All adverse events were Grade 1 injection site reactions (ISRs). The 2000 mu g dose group achieved the highest median anti-survivin IgG titre (1:327,680) at the end of the study (EOS) and a median ELISpot T cell response of 1282 SFU per million cells on day 22. Disease stabilisation (SD) was observed in 6 of 12 patients (50%), including all 3 patients (100%) in the 2000 mu g group, some of which were stabilisations of limited duration. Based on these findings, the 2000 mu g dose was selected for further evaluation in phase 1b. Interpretation OVM-200 is well tolerated and induces a robust humoral response, with a considerable cellular response and preliminary evidence of disease stabilisation. Phase 1b is ongoing to further evaluate its safety and efficacy at the selected dose. Funding Oxford Vacmedix UK Ltd. Copyright (c) 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
The QuinteT recruitment intervention and its role in oncology randomised controlled trials
No full textASPIRE for excellence in student assessment: developing a quality programme of assessment
No full textA critical component of all programmes of instruction in Medical and Health Professions Education (MHPE) disciplines is the assessment of learning and assurance of clinical competency, spanning knowledge, clinical/technical performance skills, and professionalism. AMEE's ASPIRE-to-Excellence assessment framework draws together a series of key, evidence-based components of comprehensive assessment systems, providing a matrix to 'assess assessment' through the following stimulus questionsHow does an assessment programme serve and support the mission of the institution and the goal of MHPE globally in enhancing and improving the health of both populations and individuals?Does the assessment programme support, enhance, and create learning opportunities?How does the assessment programme ensure the competence of students as they progress?How is the assessment programme subject to a rigorous and continuous quality control process?How does the assessment programme demonstrate a commitment to scholarship and innovation, including the dissemination of good practice? In this paper, these elements are detailed together with descriptions of strategies that align with how each can be successfully demonstrated and evidenced. Drawing on details of assessment practices seen in a range of submissions to the ASPIRE award programme, from a range of jurisdictions and settings, the paper highlights strategies that align with success for excellence in assessment
Breast composition and dose deposition to fat and fibroglandular tissues are associated with breast side effects after radiation therapy
No full textOBJECTIVE: Breast comprises different tissues with potentially different dose responses to radiation therapy (RT). This study investigates the correlation between RT dose, breast composition, and side effects from breast RT. MATERIAL/METHODS: Data from 922 early-stage breast cancer patients who underwent breast-conserving surgery and RT from the REQUITE study were included. Breast pain, oedema, atrophy, and induration were assessed immediately post-RT, one-year, and two-years post-RT. Maximum severity scores for each toxicity were used for analysis. Breast tissue was divided into"fat" and"fibroglandular" substructures from computed tomography (CT) using a Gaussian Mixture Model. The correlation between breast characteristics, toxicity, dosimetric parameters, and patient and clinical variables was investigated using ordinal regression. The model's fit was evaluated using the Akaike Information Criterion in SPSS v.29. RESULTS: Breast volume and breast density were associated with increased risk of breast oedema, atrophy, and induration in multivariable analysis (p<0.05). Higher mean dose and dose uniformity were observed for fibroglandular compared to fatty tissue at all severity levels, while there was no significant difference in the maximum dose to either substructure. Higher dose deposit to fat was associated with breast pain and oedema, while breast atrophy and induration were associated with dose to fibroglandular tissue. All best-performing toxicity models included dosimetric parameters derived from breast composition. CONCLUSION: Breast characterisation offers new insight into the link between dose and toxicity. Breast density and dose parameters from different substructures were associated with different breast toxicity. These findings further support the importance of dose homogeneity of breast RT planning
Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: results from SERENA-1
No full textBACKGROUND: Camizestrant, the next-generation oral selective estrogen receptor degrader and complete estrogen receptor (ER) antagonist, has previously demonstrated superiority over fulvestrant in patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Capivasertib is a selective AKT inhibitor recommended with fulvestrant for patients with PIK3CA/AKT1/PTEN-altered ER-positive, HER2-negative advanced breast cancer. Here, we report data from Parts I and J of SERENA-1 (NCT03616587), evaluating the safety, tolerability, pharmacokinetics and efficacy for the combination of camizestrant and capivasertib. PATIENTS AND METHODS: SERENA-1 is a phase I, open-label, multi-part trial of camizestrant alone and in combination with other anticancer agents in women with ER-positive, HER2-negative advanced breast cancer. In parts I and J, participants received oral camizestrant 75 mg (once daily) in combination with oral capivasertib 400 mg (4 days on, 3 days off). RESULTS: Participants (n = 29) had a median of two previous lines of therapy in the advanced setting; 55.2% had received fulvestrant and 89.7% had received a cyclin-dependent kinase 4/6 inhibitor. Camizestrant in combination with capivasertib had a well-tolerated safety profile, with diarrhea (75.9%) and nausea (44.8%) being the most common adverse events. Median t(max) was achieved ∼4 hours and ∼2 hours post dose for camizestrant and capivasertib, respectively. Clinical benefit at 24 weeks was seen in 51.7% of participants, and median progression-free survival was 8.3 months. CONCLUSION: In these pretreated participants, camizestrant 75 mg in combination with capivasertib 400 mg was well tolerated, with a side effect profile consistent with each drug as monotherapy, and showed encouraging evidence of clinical efficacy
Peritoneal metastasis histological grade independently predicts outcome in pseudomyxoma peritonei treated with curative surgery
No full textBackground Pseudomyxoma Peritonei is characterised by peritoneal metastasis from appendiceal mucinous neoplasms (AMN). The PSOGI classification (2016) categorises PMP into acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), and high-grade mucinous carcinoma peritonei (HGMCP). This study aimed to determine long-term prognosis based on this classification. Materials and methods Pathology review from PMP patients with AMNs undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) with curative intent over a 15-year period (2006-2021) was undertaken. Patients underwent standardised surveillance. Cox proportional hazards regression models, log-rank test, and Kaplan-Meier method were used to assess overall (OS) and disease-free survival (DFS) based on histopathological peritoneal metastasis grade. DFS was only calculated for patients who had a complete cytoreduction. Results 290 PMP patients were identified (AM = 34%, LGMCP = 59%, HGMCP = 7%) with median follow-up of 49 months. Median age was 59 years (range: 22-79), M: F of 1:2.5, peritoneal cancer index median of 18 (range: 0-39). Univariate OS hazard ratio (HR) is 2.75 for LGMCP vs AM (95% CI: 1.05 -7.21, p < 0.040) and 14.29 for HGMCP vs AM (95% CI: 3.92- 52.11, p < 0.001). DFS HR = 5.15 for LGMCP (95% CI: 2.19-12.10, p < 0.001) and 4.16 for HGMCP (95% CI: 1.03-16.80, p < 0.045) with an overall peritoneal metastasis p value < 0.001. Multivariate OS analysis showed that peritoneal histology for HGMCP remained a significant predictor of poor prognosis for OS (HR: 5.54, 95% CI: 1.32-23.25, p = 0.019), whilst LGMCP did not demonstrate a significant association (HR: 1.59, 95% CI: 0.59-4.26, p = 0.359). Discussion Peritoneal metastasis histopathological grade predicts outcome for patients with PMP from AMN following CRS + HIPEC independent of primary histology
Trajectories and risk factors for long-term breast symptoms following breast-conserving surgery and radiotherapy: a single centre analysis
No full textPurpose Long-term breast symptoms (pain, sensitivity, swelling and skin problems) after breast cancer treatment can affect survivors' quality-of-life. The trajectory of breast symptoms over time and risk factors associated with their development are not well understood. Methods This study built on the work of the international prospective REQUITE cohort study. Patients who underwent breast-conserving surgery and adjuvant radiotherapy (+/- chemotherapy) completed the EORTC-QLQ-BR23 questionnaire items relating to breast symptoms at four timepoints up to 24 months following radiotherapy. Patients at were re-contacted to complete additional psychometric questionnaires on different aspects of pain perception and the Hospital Anxiety & Depression Scale (HADS), with 237 respondents. Results Average breast symptoms peaked on completion of radiotherapy but returned to levels equal to or below baseline by 24 months. Patients with more severe breast symptoms at baseline continued to have worse symptoms long-term. In multivariable mixed models, higher breast symptom scores were associated with smoking (p = 0.036), any analgesic use at baseline (p = 0.005), and post-operative haematoseroma (p = 0.034), while older age and use of intensity modulated radiotherapy (IMRT) were protective (p = < 0.001 and p = 0.045 respectively). Psychometric questionnaire scores for life interference and pain severity perception were associated with persistently increased breast symptoms at 24 months on multivariable analysis, while anxiety (as determined by HADS) was associated on univariable analysis. Conclusions and implications for cancer survivors This study identifies several risk factors for persistent breast symptoms including younger age, smoking, and post-operative haematoseroma. This particularly highlights the importance of smoking cessation and use of IMRT in women at higher risk of side effects
Advanced ampullary cancer: post-hoc analysis of the ABC-01, ABC-02, and ABC-03 clinical trials
No full textAmpullary carcinoma (AC) is a rare malignancy. It is often classified within biliary tract cancers (BTC) but lacks dedicated treatment guidelines. This post-hoc analysis evaluated outcomes of patients with advanced AC enrolled in the ABC-01, ABC-02, and ABC-03 clinical trials to provide reference data for future studies. All patients with advanced AC formed the"Descriptive cohort," while those AC treated with cisplatin-gemcitabine (CisGem) comprised the"CisGem-treated cohort." Among 534 trial participants, 28 (5.24%) had AC, and 17 received CisGem. The median age was 63.93 years, and 75.00% were male. Most patients had metastatic disease at baseline (89.29%). Median follow-up for the CisGem-treated cohort was 10.23 months (95% CI 5.98-14.43). The objective response rate was 23.52%, and disease control was achieved in 58.82% of patients. Estimated median progression-free survival (PFS) and overall survival (OS) were 7.98 months (95% CI, 6.86-8.44) and 11.76 months (95% CI, 5.94-14.88), respectively, comparable to outcomes in other BTCs. No reliable prognostic or predictive factors for PFS, OS, or ORR were identified, likely reflecting the small sample size. This analysis underscores the rarity of advanced AC and the challenges in recruiting adequate numbers for dedicated trials. While CisGem remains an appropriate standard-of-care regimen, modest survival outcomes highlight the need for improved therapies. Molecular profiling has revealed potentially actionable alterations, including HER2 amplification and KRAS mutations, supporting precision oncology approaches. This study provides the most comprehensive reference dataset to date for advanced AC treated with CisGem and emphasizes the importance of international collaboration and molecularly guided research to improve outcomes in this rare malignancy