Using Breath,Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT With RayPilot® Motion Management
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- NHS Lothian
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Measurement of the relative change in normal tissue and tumour cell free DNA (cfDNA) released into the blood of men with prostate cancer treated with prostate stereotactic body radiotherapy (SBRT)
研究概览
简要总结
Personalisation of radiotherapy dose based on real-time assessments of normal tissue and tumour response would maximise cure and minimise treatment related toxicity. During a 5 fraction course of prostate Stereotactic Body Radiotherapy (SBRT) this pilot study will assess whether a number of different biomarker approaches can predict for normal tissue and tumour response. Firstly the investigators will analyse volatile organic compounds released within the breath with each fraction of treatment. Secondly the investigators will analyse cell free normal tissue and tumour DNA released during treatment. Thirdly the investigators will develop imaging processing algorithms to look for imaging biomarkers predicting rectal wall toxicity using pre and post treatment cone beam CT verification images. Each of these approaches will be assessed against prostate specific antigen (PSA), Common Terminology Criteria for Adverse Events (CTCAE v4.0) criteria and Expanded Prostate Cancer Index Composite (EPIC-26) patient reported outcomes with a maximum of 24 months of follow up.
详细描述
Radiotherapy scheduling and prescription dose does not take into account individual patient heterogeneity in normal tissue response or tumour response. Personalisation of radiotherapy dose based on real-time assessments of normal tissue and tumour response would maximise cure and minimise treatment related toxicity. During a 5 fraction course of prostate Stereotactic Body Radiotherapy (SBRT) this pilot study will assess whether a number of different biomarker approaches can predict for normal tissue and tumour response. Firstly the investigators will analyse volatile organic compounds released within the breath with each fraction of treatment using Gas Chromatography Ion Mobility Spectroscopy (GC-IMS). The investigators have extensive experience in this area within the TOXI-Triage research program (www.toxi-triage.eu/) including deep learning and machine learning techniques to interrogate the metabolomics data generated. Secondly the investigators will analyse cell free normal tissue and tumour DNA released during treatment to assess both tumour and normal tissue response. Radiotherapy releases large amounts in to the blood stream allowing easier quantitative analysis. Thirdly the investigators will look for imaging biomarkers of rectal wall toxicity using imaging analysis algorithms of on-treatment cone beam verification CT images taken before and after each radiotherapy treatment. The RayPilot® system made by Micropos Medical Ltd tracks prostate motion throughout the SBRT delivery to ensure that the treatment dose is delivered with great precision. The potential of each biomarker approach for predicting normal tissue and tumour response will be assessed against PSA and CTCAE v 4.0 toxicity criteria and EPIC-26 patient reported outcome measures after 24 months of patient follow up.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Low risk prostate cancer T1-2, PSA<10ng/ml, Gleason score (GS) 3+3=6
- •Intermediate risk prostate cancer T1-T2, PSA 10-20ng/ml,GS ≤7(3+4=7 only)
- •World Health Organisation (WHO) performance status 0-2
- •Prostate volume ≤90cc
- •International Prostate Symptom Score (IPSS) ≤20
- •Peak urinary flow rate (Q-max) >10cc/sec
- •Urinary residual <250mls total
- •No prior Trans Urethral Resection of the Prostate (TURP)
- •No previous pelvic radiotherapy
- •Able to give informed consent
- •Aged between 18-85 years of age
排除标准
- •Inflammatory bowel disease
- •Previous androgen deprivation therapy
- •History of urinary retention
结局指标
主要结局
Measurement of the relative change in normal tissue and tumour cell free DNA (cfDNA) released into the blood of men with prostate cancer treated with prostate stereotactic body radiotherapy (SBRT)
时间窗: pre treatment before each fraction of SBRT day 1 to day 5, then at 1 and 3 hours post treatment day 1 to day 5
Change in the density of 90-150 base pair fragment size cfDNA from baseline pre-treatment to completion of SBRT for each time point, for each patient
Measurement of the relative change in Gas Chromatography Ion Mobility Spectra (GC-IMS) of Volatile Organic Compounds (VOC's) from breath samples of men with prostate cancer treated with prostate stereotactic body radiotherapy (SBRT)
时间窗: pre treatment before each fraction of SBRT day 1 to day 5, then at 1 and 3 hours post treatment day 1 to day 5
Measurement of the change in the 3D chromatogram of volatile organic compound GC-IMS Spectra detected from baseline pre-treatment, to completion of SBRT at each time point, for each patient. Each 3D chromatogram GC-IMS printout is generated from the readings of each axis. The y axis is associated with GC separation of VOC's, the x axis measures the movement of the generated ions (IMS drift time) and the z axis ion detector response equating to concentration. These 3 values separate, identify and quantify the VOC compounds detected.
Measurement of the true rectal wall delivered radiation dose compared to planned dose during the prostate SBRT for each patient
时间窗: Immediately pre each fraction of SBRT day 1 to 5 and immediately post each fraction of SBRT day 1 to 5
Dose calculation in cGy between expected and observed actual dose to the rectal wall using pre and post each fraction radiotherapy linear accelerator treatment verification cone beam CT scans
次要结局
- Measurement of SBRT treatment related quality of life(Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment)
- Measurement of SBRT treatment related acute and late normal tissue toxicity(Baseline, completion of SBRT, week 6, then 3 months, 6 months, 12 months, 18 months and 24 months post treatment)