The Christie School of Oncology: Christie Research Publications Repository
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Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT part c: a phase Ib trial
No full textAtaxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. In this study, we explore the combination of the ATR inhibitor, ceralasertib, and palliative radiotherapy, with primary endpoint the identification of maximum tolerated dose, and secondary endpoints the determination of adverse event causality, pharmacokinetics (PK) and anti-tumor activity. Twenty-seven patients were dosed in escalating dose cohorts from 20 to 80 mg twice daily (BD) with concomitant radiation, 20 Gy in 10 fractions or 30 Gy in 15 fractions. Patients were assessed for acute and late toxicities and response after therapy. A non-tolerated dose was not reached. Maximum administered dose was 80 mg BD ceralasertib over 3 weeks with 30 Gy in 15 fractions, at which 1/6 evaluable patients had dose-limiting toxicities (radiation dermatitis and mucositis). PK was comparable to monotherapy. Of 23 efficacy-evaluable participants, 2 (9%) had complete response (CR), 6 (26%) partial response (PR), 13 (57%) stable disease (SD) and 2 (9%) progressive disease (PD) as best response in irradiated tumors. Response was not clearly linked to genomic aberrations. Increased T and natural killer cell activation as observed in peripheral blood as treatment progressed
Application of causal inference techniques for accurate estimation of the causal effect of dose to the heart base on overall-survival in lung cancer
No full textAccelerated Hypofractionated Radiotherapy for Locally Advanced NSCLC: A Systematic Review From the International Association for the Study of Lung Cancer Advanced Radiation Technology Subcommittee
No full textIntroduction: Accelerated hypofractionated radiotherapy has gained increasing interest for locally advanced NSCLC, as it can potentially increase radiobiologically effective dose and reduce health care resource utilization. Nevertheless, there is sparse prospective evidence supporting routine use of accelerated hypofractionation with or without concurrent chemotherapy. For this reason, the International Association for the Study of Lung Cancer Advanced Radiation Technology Subcommittee conducted a systematic review of prospective studies of accelerated hypofractionation for locally advanced NSCLC. Methods: A systematic search was conducted on Ovid MEDLINE, Ovid EMBASE, Wiley Cochrane Library, and ClinicalTrials.gov for English publications from 2010 to 2024 for prospective clinical trials and registries investigating accelerated hypofractionated radiotherapy defined as more than 2 Gy delivered in 10 to 25 fractions for non- metastatic locally advanced (stage III) NSCLC. Results: There were 33 prospective studies identified that met the criteria for inclusion. Of 14 prospective studies evaluating definitive accelerated hypofractionation (without concurrent chemotherapy), there were six prospective registries, seven phase 1 to 2 trials, and one phase 3 randomized clinical trial, with a median dose of 60 Gy delivered in a median of 16 fractions, median progression-free survival of 6.4 to 25 months, median survival of 6 to 34 months, and 0% to 8% severe grade >= 3 esophagitis. There were 19 studies evaluating accelerated hypofractionated chemoradiation with platinum doublet-based chemotherapy as the most common concurrent regimen. Of these accelerated hypofractionated chemoradiation studies, there were 18 phase 1 to 2 trials and one prospective registry with a median radiation dose of 61.6 Gy delivered in a median of 23 fractions, median progression-free survival of 10 to 25 months, median survival of 13 to 38 months, grade >= 3 esophagitis of 0% to 23.5%, and grade >= 3 pneumonitis of 0% to 11.8%. Conclusions: Despite the increasing use of accelerated hypofractionation for locally advanced NSCLC, the sup- porting randomized evidence remains sparse. Only one randomized clinical trial comparing 60 Gy in 15 fractions with 60 Gy in 30 fractions without concurrent chemo- therapy did not reveal the superiority of accelerated hypofractionation. Therefore, the use of accelerated hypofractionated radiotherapy should be approached with caution, using advanced radiation techniques, espe- cially with concurrent chemotherapy or targeted agents. Accelerated hypofractionated radiotherapy should be carefully considered alongside other multidisciplinary options and be further investigated through prospective clinical trials. (c) 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies
NETWORK META-ANALYSIS NMA OF CLINICAL EFFECTIVENESS OF SECOND-LINE (2L+) TREATMENTS IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC)
No full textSurvival and radiotherapy-related adverse events in patients receiving radiotherapy and concurrent metformin: a systematic review and meta-analysis of randomised controlled trials and cohort studies
No full textBackground: It remains unclear whether metformin, a widely used antidiabetic medication, has any influence on the survival outcomes or treatment-related toxicities of radiotherapy in cancer patients. Given metformin's potential anti-cancer properties, including its ability to inhibit tumour growth through the modulation of cellular metabolism and enhancement of radiosensitivity, its impact on radiotherapy outcomes warrants thorough investigation. This study aimed to evaluate the impact of metformin on survival and adverse events among cancer patients receiving radiotherapy. Methods: Database searches were conducted in MEDLINE, EMBASE, Web of Science, Scopus, and PubMed (2000-2025) to retrieve studies of adults with cancer treated with radiotherapy and concurrent metformin. Metformin users were compared with non-users. The pooled overall survival rate was presented in terms of odds ratio (OR) and 95% confidence interval (95%CI). Diabetic subgroup analyses and meta-regression by cancer type were conducted. ORs and 95%CIs of radiotherapy-related adverse events were presented by cancer type. Results: This study identified 25 articles. The pooled overall survival rate showed no significant difference between metformin users and non-users across subgroups (ORs: 1.00-1.77). Conflicting survival trends were observed for prostate, oesophageal, and non-small cell lung cancer across diabetic conditions. Metformin users with breast cancer exhibited a significantly lower risk of heart failure (OR: 0.72; 95%CI: 0.56-0.94) and heart events (OR: 0.72; 95%CI: 0.59-0.88). Conclusions: Metformin did not significantly impact overall survival but may reduce heart-related adverse events in breast cancer patients based on limited data. Further research is needed on cancer types and diabetic conditions
Results of a phase 1 study of vosilasarm (EP0062), a first-in-class oral selective androgen receptor modulator (SARM) in patients with advanced or metastatic AR+/ER+/HER-2-breast cancer
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Estimating the carbon footprint of an international radiation oncology conference and modelling reduction strategies
No full textBACKGROUND AND PURPOSE: Healthcare professionals attend international meetings to network, disseminate science and update practice. Conferences have large carbon footprints, and this study aimed to estimate the carbon footprint of an ESTRO conference and potential reduction strategies while balancing needs of international networking. MATERIALS AND METHODS: The geographical distribution of ESTRO23 attendees was used. The Climatiq API was utilised to determine the carbon footprint, in kg CO(2) equivalent (CO(2)e), of venue, accommodation and travel. The impact of venue location and train travel on total CO(2)e was estimated as well as impact of online attendance. The amount and impact of in-person networking was assessed through a post conference survey. RESULTS: The carbon footprint of ESTRO 2023 was 1.4 tCO(2)e per attendee. Centrally located venues had lowest travel carbon footprint, e.g. Frankfurt with 8,873 tCO(2)e was 28 % lower than Lisbon. Hotel and venue accounted for 95 % (81 % from long-haul flights). Centrally located venues and train travel are important means of reducing CO(2)e. The amount of international networking varies considerably across attendees, and regional or online participation can potentially reduce CO(2)e without compromising conference output for some attendees
Decrease in fracture rate with mandatory bone-protecting agents in the EORTC 1333/PEACE-3 trial comparing radium-223 combined with enzalutamide versus enzalutamide alone: a safety analysis
No full textBone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available. Here we publish for the first time fracture rates from an interim safety analysis of the international prospective phase 3 PEACE-3 trial comparing radium-223 ((223)Ra) combined with enzalutamide for first-line mCPRC to enzalutamide alone. After results from the ERA-223 trial (abiraterone ± (223)Ra) showed a high fracture rate in both arms, the independent data monitoring committee of PEACE-3 mandated BPA use during the trial, which increased BPA use from 46.1% to 97%. For patients who received BPA therapy, fracture rates significantly decreased in both study arms. At 1 year, fractures decreased from 15.6% to 2.6% with a BPA in patients receiving enzalutamide monotherapy. The interim safety analysis of PEACE-3 underscores the high risk of fracture in patients with mCRPC and the necessity of complying with guidelines regarding BPA administration in the ARPI era. The EORTC GUCG-1333 PEACE-3 trial is registered on ClinicalTrials.gov as NCT02194842 and on EudraCT as 2014-001787-36
Systemic anti-cancer therapy and anaesthesia: a narrative review
No full textINTRODUCTION: Cancer research has revolutionised the treatment, quality of life and life expectancy of people living with cancer. Systemic anti-cancer treatments have expanded to involve not only cytotoxic drugs, but targeted drugs and immunotherapy. Although highly effective in many patients, these drugs can cause serious and sometimes life-threatening adverse reactions. As part of their treatment, many patients living with cancer will be offered both systemic anti-cancer therapy and surgery, and many patients will undergo recurrent episodes of both with the aims of cure, palliation or prolongation of life expectancy. It is important for anaesthetists to understand the effects of systemic anti-cancer therapy on their patients. METHODS: An electronic literature search using was conducted in May 2024 for peer-reviewed articles in English. An initial search of the terms 'anaesthesia' and 'chemotherapy' revealed that existing review literature was tailored towards the neoadjuvant setting and prompted this review to include the complications of targeted therapies, emergency care and intra-operative administration of systemic anti-cancer therapy to reflect this evolving field. A narrative approach was taken to discuss common regimens and their complications. RESULTS: The review encompasses a wide range of sub-topics including pharmacology; physiology; peri-operative medicine; specialist surgery; adverse events; and safety. Data from multicentre trials that form the basis of current treatment regimens and practice were prioritised during the selection process. Smaller studies, case series and case reports were included to illustrate the rarer but clinically significant adverse effects of specific therapies. CONCLUSIONS: It is important for anaesthetists to have a comprehensive understanding of the effects of systemic anti-cancer therapies, including cytotoxic and immunotherapies. There are many potential toxicities and complications associated with these treatments, particularly in the context of emergency surgery and the administration of cytotoxic drugs within the operating theatre environment