Evaluation of the mechanism of action and responses to Prostate Brachytherapy

Project aims

​​Brachy TRACKS Study  

​Primary Objectives : 

  • To measure biochemical changes in a panel of metabolites (e.g. lipids, glycogen, amino acids) implicated in radiation response pathways to determine intra- and inter-patient heterogeneity of dose response and to correlate to clinical response. 
  • ​To identify patient-specific clonal somatic mutations from prostate biopsy tissue and to determine if a single fraction of high-dose radiation is associated with a transient increase in abundance of circulating tumor DNA in peripheral blood plasma.
  • ​To evaluate the changes in immune response to BT by scRNA-sequencing and to determine the potential mutations that can elicit T cell responses.
  • To determine the extent of microbial composition before and after BT and correlate with immune activation and metabolic changes (Aim 1 & 3). 

​Secondary Objectives: 

  1. ​Response outcomes: 
    • ​PSA nadir: recorded every 6 months to 5 years and then annually to 10 years.
    • ​4-year PSA < 0.2 ng/ml (indicative of cure)
  2. Acute and long term toxicity graded using Common Terminology Criteria for Adverse Events (CTCAE) v5 

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​MONO Study 

​Primary Objective :  

  • To evaluate the difference in Quality of Life (QO) in the urinary domain between LDR and HDR brachytherapy.  

​Secondary objectives: 

  • ​Quality of Life scores in the bowel and sexual domains and International Prostate Symptom Scores  
  • ​Acute and long-term toxicity, graded using the Common Terminology Criteria for Adverse Events (CTCAE V4) 
  • ​TRUS- MRI fusion will be developed within our planning software to facilitate treatment planning
  • ​Two standard predictors of outcome to assess treatment efficacy;
    • ​PSA nadir 
    • ​Prostate re-biopsy will be performed to assess the local efficacy of radiation. 
  • MRI-TRUS fusion accuracy will be verified by targeted biopsies prior to each brachytherapy procedure (LDR or  HDR). 
  • ​Biopsy material for subsequent genetic testing to determine Cell cycle Progression scores to ultimately correlate with outcome.

 

Anticipated outcomes and impact

​​The Brachy TRACKS study is actively recruiting participants to investigate the ways High Dose Rate (HDR) brachytherapy treatment affects the tumour in patients with localized prostate cancer. HDR brachytherapy is a type of prostate brachytherapy that involves radioactive sources travelling through needles that have been temporarily inserted into the prostate. HDR Brachytherapy is a very precise form of prostate radiation that is associated with faster symptom recovery compared to seed implant Low Dose Rate (LDR) Brachytherapy. Prostate biopsy samples are collected prior to treatment.  This study will look at the different types of responses, such as biological, chemical and cell responses, that happen after HDR brachytherapy and are linked with how cancer responds to the treatment.  The study will also look at how the dose of radiation within the prostate is related to tumour responses. This study help to understand how HDR brachytherapy compares to other forms of radiation for localized prostate cancer. We will compare the average length of time after treatment that a person lives without cancer coming back and any immediate and long term side effects.   

​The MONO study is has completed enrolment and participants are in long term follow up. It is a randomized study comparing the 2 types of brachytherapy (LDR versus HDR) when used alone, without the addition of external radiation. This study aims to determine if there are any advantages of one type over the other, specifically in how quickly men recover from their treatment. Participants on the study were offered optional participation in collecting biopsy samples. These samples are analyzed to better understand how prostate cancer responds to brachytherapy. Avanced imaging techniques were used to be able to see the location of cancer within the prostate. Prostate biopsy samples were collected prior to treatment. A portion of the samples are sent for testing of the genetic profile of the tumor (Cell Cycle Progression Score) which has been shown to correlate with how aggressive the cancer is. The results of this test will show if there is a difference in how tumours respond to the 2 types of brachytherapy based on their Cell Cycle Progression Score. This may be useful in the future to other men with prostate cancer to help determine the best treatment for them.

Key Researchers