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Use of ventilation techniques to improve radiotherapy dose distributions in patients with thoracic and upper abdominal tumours

ABSTRACT: Interventions: Continuous Positive Airway Pressure (CPAP) will be used in patients receiving stereotactic ablative body ratiotherapy (SABR) to any tumour in the lung or upper abdomen. This will be delivered by sleep scientists, radiation therapists, radiation oncologists and medical physicists. The patients will have CPAP at radiotherapy simulation session, in which a four dimensional computed tomography (4DCT) scan is acquired without CPAP, followed by a 4DCT acquired with CPAP. The simulation session will take approximately 30 mins. The CPAP will be applied using room air, ramping up from 4 cmH2O to a maximum pressure of 20 cmH2O, depending on participant tolerance, over a period of 5 mins. The time between 4DCT acquisitions will be the CPAP pressure ramp up time, 5 mins. We will then measure the effect of CPAP on tumour motion based on the tumour visualised in the 4DCTs. If tumour motion is reduced with CPAP, the patient will have CPAP for the duration of each of their radiotherapy treatment sessions (1-5 sessions). Primary outcome(s): Tumour motion (Euclidian distance between inhale and exhale phases) when CPAP is used and with free breathing as measured on 4DCTs[At the simulation session] Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Type of endpoint: Efficacy

DISEASE(S): Lung Cancer,Cancer-any Cancer,Colorectal Cancer,Kidney Cancer,Breast Cancer

PROVIDER: 2470180 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Muscle-invasive bladder cancer (MIBC) is a prevalent disease that can be treated with radiotherapy, but has a poor prognosis. Radiation-induced extracellular matrix (ECM) remodelling and fibrosis can induce tumour resistance and recurrence, but have not been studied in MIBC. Here, we aimed to characterise the impact of radiation on the ECM composition of MIBC. Three MIBC cell lines (T24, UMUC3, J82) were treated with fractionated radiation. We used proteomics to analyse the ECM composition produced by surviving cancer cells and immunofluorescence to investigate changes in the morphology and number of ECM fibres. We evaluated the RNA expression of identified ECM proteins (FN1, COL5A1, COL1A1, TNF6AIP6, FLG) in one cystectomy (TCGA-BLCA, n=397) and two radiotherapy (BC2001, n=313; BCON, n=151) cohorts. There were 613 proteins affected by radiation (padj<0.05, fold change >2 or <-2), 68 of which were ECM-associated proteins. There was a general increase in proteases and protease regulators but heterogeneity across cell lines. Enrichment analysis showed ECM organisation was the primary pathway affected. Immunofluorescence confirmed radiation affected ECM structure, generally, reducing the number, length and width of fibres. Five ECM genes of interest were identified (COL1A1, COL5A2, FN1, FLG, TNFAIP6), constituting an ECM signature. High FN1, COL1A1, TNF6AIP6 mRNA levels and ECM signature scores were independent poor prognostic markers, while FLG mRNA expression independently predicted radiotherapy benefit in a meta-analysis (n=861). We found high COL1A1 expression levels predicted hypoxia-modifying treatment benefit. Prognostic significance of COL5A2, FN1 and the ECM signature was dependent on patients harbouring TP53-mutations. Radiation alters the composition and structure of the ECM produced by MIBC. As a proof-of-concept, we showed that radiation-affected ECM genes are independent prognostic and predictive markers of radiotherapy benefit in MIBC. Future studies should validate these radiation-induced ECM changes in clinical samples, and explore the role of FLG in radioresistance.

Project description:Interventions: Cohort: 10 patients with histologically proven squamous cell carcinoma (SCC) of the anus, presenting to Austin Health for chemo-radiotherapy from June 2015. Observation: for up to 3 years post-radiotherapy. Interventions additional to standard procedures for purpose of study are administered by qualified health professionals and include: Pre-radiotherapy imaging: During standard MRI imaging session – non-standard diffusion weighted MRI (dwMRI) and dynamic contrast enhanced (DCE) MRI scans within Radiology facility. During standard CT simulation session – additional CT scan in prone position within Austin Radiation Oncology. Post-Radiotherapy - 3-4 weeks post completion of radiotherapy - non-standard timepoint for these scans MRI session – including dwMRI and DCE MRI scans within Radiology facility. PET session - PET imaging within Austin Nuclear & Molecular Imaging department. A number of imaging scans are required to map disease for targeting of radiotherapy (RT), including CT, PET and MRI. Each provides slightly different information about the position, shape and composition of the disease that is used by a Radiation Oncologist to define where to target the radiation and how much radiation to deliver. We aim to add an extra, non-standard MRI imaging sequence called a diffusion weighted (dwMRI) scan, to understand the characteristics of the disease and how its use may change the size or shape of the target area so as to ensure complete treatment coverage and improved outcomes from treatment. Additionally, the use of contrast with MRI, dynamic contrast enhanced MRI (DCEMRI) has been shown in other cancer sites to help better identify and show the disease and to show response to treatment, and we wish to verify this in anal Primary outcome(s): Identify the differences in radiotherapy target volume definition on standard (CT, T1/T2 MRI and PET) versus non-standard imaging modalities (dwMRI & DCE-MRI).[2 years post-radiotherapy] Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group

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Use of ventilation techniques to improve radiotherapy dose distributions in patients with thoracic and upper abdominal tumours

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