The Christie School of Oncology: Christie Research Publications Repository
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Preliminary dose-volume constraints predicting subcutaneous tissue fibrosis for limb sarcoma using the VorteX and IMRiS trials
No full textMultidimensional fatigue and its impact on work productivity, mood and quality of life in long-term survivors following definitive intensity-modulated radiotherapy for oropharyngeal cancer: a cross-sectional study
No full textPURPOSE: Radiotherapy (RT) for oropharyngeal cancer (OPC) can lead to late toxicity. Fatigue is a known debilitating issue for many cancer survivors, yet prevalence and severity of long-term fatigue in patients treated for OPC is unknown. METHOD: As part of a mixed-methods study, fatigue in OPC patients ≥ 2 years post RT + / - chemotherapy was evaluated. Fatigue scores (multidimensional fatigue inventory; MFI) were compared to general population controls. Predictive sociodemographic/clinical factors of fatigue were investigated by multivariable linear regression. Associations between fatigue, health related quality of life (EQ-5D-5L), work (work productivity and activity impairment - WPAI), mood disturbance (Profile of Mood Scale - POMS) and RT dose were explored. RESULTS: In 349 patients treated for OPC with median follow-up time post-RT (+ / - chemo) of 6 years (IQR 4-8), > 20% reported severe fatigue in all domains. Scores were significantly worse in patients for mental (mean difference 1.2, 95% CI 0.6-1.8, p = < 0.001) and general fatigue (mean difference 0.8, 95% CI 0.1-1.3, p = 0.015) compared to controls. Age and co-morbidities were significant predictors of mental and general fatigue (p < 0.05). Worse fatigue was associated with worse quality of life, greater work productivity impairment and worse mood (r = - 0.604, 0.582 and 0.679, respectively, all p < 0.05). No correlation was found between fatigue and RT dose to the posterior fossa. CONCLUSIONS: Mental and general fatigue remain significant issues in OPC patients several years after RT + / - chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: Better monitoring of fatigue throughout follow-up care, and timely interventions could help improve patient functioning
Feasibility and acceptability of using electronic patient-reported outcome measures (ePROMs) in follow-up care after radiotherapy
No full textImpact of therapeutic X-ray exposure on collagen I and associated proteins
No full textBiological tissues are exposed to X-rays in medical applications (such as diagnosis and radiotherapy) and in research studies (for example microcomputed X-ray tomography: microCT). Radiotherapy may deliver doses up to 50Gy to both tumour and healthy tissues, resulting in undesirable clinical side effects which can compromise quality of life. Whilst cellular responses to X-rays are relatively well-characterised, X-ray-induced structural damage to the extracellular matrix (ECM) is poorly understood. This study tests the hypotheses that ECM proteins and ECM-rich tissues (purified collagen I and rat tail tendons respectively) are structurally compromised by exposure to X-ray doses used in breast radiotherapy. Protein gel electrophoresis demonstrated that breast radiotherapy equivalent doses can induce fragmentation of the constituent α chains in solubilised purified collagen I. However, assembly into fibrils, either in vitro or in vivo, prevented X-ray-induced fragmentation but not structural changes (as characterised by LC-MS/MS and peptide location fingerprinting: PLF). In subsequent experiments exposure to higher (synchrotron) X-ray doses induced substantial fragmentation of solubilised and fibrillar (chicken tendon) collagen I. LC-MS/MS and PLF analysis of synchrotron-irradiated tendon identified structure-associated changes in collagens I, VI, XII, proteoglycans including aggrecan, decorin, and fibromodulin, and the elastic fibre component fibulin-1. Thus, exposure to radiotherapy X-rays can affect the structure of key tissue ECM components, although additional studies will be required to understand dose dependent effects. STATEMENT OF SIGNIFICANCE: Biological systems are routinely exposed to X-rays during medical treatments (radiotherapy) and in imaging studies (microCT). Whilst the impact of ionising radiation on cells is well characterised, the interactions between X-rays and the extracellular matrix are not. Here, we show that relatively low dose breast radiotherapy X-rays are sufficient to affect the structure of collagen I in both its solubilised and fibrillar forms. Although the impact of intermediate X-ray doses on extracellular proteins was not determined, the high dose exposures which are achievable using a synchrotron source had an even greater effect on the structure of collagen I molecules and, in tendon, on the structures of many accessory extracellular matrix proteins, The unwanted side effects of radiotherapy may therefore be due to not only cellular damage but also damage to the surrounding matrix
International expert consensus on the clinical integration of circulating tumor cells in solid tumors
No full textBackground: Circulating tumor cells (CTCs) are a versatile biomarker in solid tumors. Extensive research supports their clinical relevance and led to regulatory approval in breast, prostate, and colorectal cancers. However, clinical adoption remains limited mainly due to the lack of consensus and standardized technologies. Additionally, CTC research lacks unified direction. To address these gaps, an international expert panel was established to assess the current and future clinical utility of CTCs. Methods: A panel of 11 CTC experts identified key areas of controversy, informing a structured survey distributed to 55 international multidisciplinary experts. Consensus was predefined as >= 70 % agreement. Areas without consensus were discussed in a virtual meeting, leading to final statements on the clinical integration of CTCs. Results: Thirty-seven experts completed the survey. Consensus was reached on the clinical utility of CTCs for prognosis and treatment monitoring in metastatic breast (BC) and prostate (PC) cancers, including AR-V7 testing in metastatic castration-resistant PC for therapy selection. In other tumors, CTCs remain investigational. Experts agreed that while clinical utility is not yet established in early-stage disease, CTCs show promise in early BC, especially combined with cell-free DNA (cfDNA) for minimal residual disease detection. CellSearch (R) is currently the only platform with high-level evidence for clinical use, though emerging technologies are promising. Key challenges include improving detection sensitivity/specificity, standardizing workflows, generating robust data, and clinician education. Experts emphasized shifting from enumeration to phenotypic and molecular characterization, particularly for treatment guidance, and highlighted the complementary role of CTCs and cfDNA, advocating for integrated liquid biopsy approaches. Conclusions: This consensus offers practical guidance for clinical integration of CTCs and outlines strategic research priorities to unlock their full potential in precision oncology
Loncastuximab tesirine in previously treated diffuse large B-cell lymphoma: a plain language summary of the LOTIS-2 study
No full textWHAT IS THIS SUMMARY ABOUT? This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.Participants received loncastuximab tesirine, also referred to as Lonca, for up to 1 year, or longer if the treatment was working, and their health was monitored. The primary purpose of the LOTIS-2 study was to find out if participants' lymphoma shrank partially or completely after receiving Lonca. WHAT WERE THE RESULTS? A total of 145 participants who were treated with Lonca lived a median (meaning the middle value in a set of numbers) of 9.5 months after starting Lonca treatment. The lymphoma shrank partially or completely in nearly half of participants and shrank completely in 1 in 4 participants. Among participants whose disease either shrank partially or completely in response to Lonca treatment, responses happened relatively quickly, with a median time to response (the time between starting treatment and when the participant's lymphoma either partially or completely shrank) of 41 days. In these participants, the lymphoma did not grow or come back for a median of 13.4 months. Researchers estimated that 83% of participants whose disease shrank completely remained disease free for at least 1 year.Nearly all participants had a side effect from Lonca treatment. The most common side effects were abnormal liver tests (increased gamma-glutamyl transferase), decreased white blood cells (neutropenia), and decreased platelets (thrombocytopenia). One in 4 participants had their treatment stopped due to side effects. The most common side effects that resulted in participants needing to stop Lonca treatment were abnormal liver tests (increased gamma-glutamyl transferase), swelling in the arms or legs (peripheral edema), swelling in an individual spot (localized edema), and fluid around the lungs (pleural effusion). WHAT DO THE RESULTS OF THE STUDY MEAN? These results show that Lonca is a treatment option with controllable side effects for many patients with DLBCL whose disease did not respond or came back after 2 or more previous treatments. For participants whose lymphoma completely shrank while taking Lonca, those responses to treatment occurred quickly and lasted for over a year
Health-related quality of life and performance status with NALIRIFOX versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma: results from the NAPOLI 3 trial
No full textBACKGROUND: In NAPOLI 3 (NCT04083235), first-line (1L) liposomal irinotecan plus 5-fluorouracil/leucovorin plus oxaliplatin (NALIRIFOX) demonstrated statistically significant improvements in overall survival and progression-free survival compared with gemcitabine plus nab-paclitaxel (Gem + NabP) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this exploratory analysis, health-related quality of life (HRQoL) and performance status (PS) outcomes from NAPOLI 3 were evaluated. MATERIALS AND METHODS: HRQoL was assessed at baseline, day 1 of each treatment cycle, and at end of treatment (EoT) using the European Organisation for Research and Treatment of Cancer Quality of Life core questionnaire (EORTC QLQ-C30). Analyses included patients who provided baseline and at least one subsequent assessment. A mixed model for repeated measures was used to describe score evolution over time between treatment arms. Eastern Cooperative Oncology Group (ECOG) PS was recorded in the intention-to-treat (ITT) population at baseline, days 1, 8, and 15 of each treatment cycle, and EoT. Time to deterioration (TTD) in EORTC QLQ-C30 and ECOG PS scores was estimated using the Kaplan-Meier methodology. RESULTS: Overall, 245 patients in the NALIRIFOX arm (ITT population, n = 383) and 232 patients in the Gem + NabP arm (n = 387) provided baseline and at least one subsequent EORTC QLQ-C30 assessment. There was an initial decline in global health status (GHS) from baseline to week 12 across both treatment arms [least-squares mean -2.4, 95% confidence interval (CI) -5.9 to 1.1; Gem + NabP: -0.7 (-4.2 to 2.9)], with no further deterioration from week 16 onwards. TTD in GHS (hazard ratio 0.74, 95% CI 0.53-1.04, nominal P = 0.08) and ECOG PS score (hazard ratio 0.72, 95% CI 0.55-0.92, nominal P = 0.009) was longer with NALIRIFOX than with Gem + NabP. CONCLUSIONS: These data suggest that 1L NALIRIFOX provides efficacy benefits for patients with mPDAC without compromising HRQoL or PS compared with Gem + NabP
Best Practice for Patient-centred Radiotherapy in Clinical Trials and Beyond-A National Multidisciplinary Consensus
No full textAIMS: Patient-centred radiotherapy refers to an approach where patients' needs and preferences are prioritised. Guidelines for this personalised approach are lacking. We present a multidisciplinary national consensus with the aim to provide recommendations for best practice in patient-centred radiotherapy for both clinical trials and routine practice. MATERIALS AND METHODS: A multidisciplinary working group was formed, comprising of healthcare professionals and patient advocates with lived experience of radiotherapy. Three interlinking themes were identified around patient-centred radiotherapy: information, decision-making, and outcomes. Scoping reviews were carried out for each theme, considering current challenges and recommendations for best practice. Recommendations were shaped through consultation with 12 patient advocates. RESULTS: There is a pressing need to better support patients prior to, during, and following radiotherapy. Radiotherapy-related patient information is often complex and challenging to understand. Information resources should be cocreated with patient advocates and individualised wherever possible, including for patients from under-served groups. Shared decision-making (SDM) processes may enhance treatment satisfaction and reduce decision-regret, but these are not widely implemented. SDM requires prepared patients, trained teams, alongside adequate resources and should be offered as per patients' preferences. Healthcare system data offer complementary information to clinical trials, with the potential to provide additional insight into long-term benefits and risks of radiotherapy within 'real-world' conditions. Patient-reported outcome measures may provide greater insight regarding toxicity and impact on quality of life and should be used in synergy with clinician-reported outcomes. Outcome measures should be collected in the long term, and results should be widely disseminated to both the public and professional communities. Equity of access to radiotherapy, clinical trials, and survivorship services is a priority. CONCLUSION: Patients rightly expect more from healthcare professionals, and it is important that the radiotherapy community recognises this and embraces changes which will enhance patient-centred care. Our recommendations aim to guide best practice for patient-centred radiotherapy
