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Exploring Genomic, Proteomic and Dosimetric Determinants of Late Toxicity After Three Dimensional Conformal Radiotherapy (RT) for Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00122265
Recruitment Status : Terminated
First Posted : July 22, 2005
Last Update Posted : February 26, 2016
Information provided by (Responsible Party):
AHS Cancer Control Alberta

Brief Summary:
Prostate cancer is the most common malignancy in males, and radiotherapy is a commonly chosen treatment option for patients with localized disease. Technical innovations such as three-dimensional conformal radiotherapy (3D CRT) and intensity-modulated radiotherapy permit radiation dose escalation and possibly better disease outcomes, but escalated doses may be accompanied by long-term complications. This study will examine, for the first time, the independent contribution of a patient's own genetic makeup to the development of post-radiation complications, permitting the future development of predictive tests to avoid radiation injury. To do this, the investigators will examine gene markers and blood proteins in a series of approximately 100 prostate cancer survivors who have received three-dimensional conformal radiotherapy between 1996 and 2000 at the Cross Cancer Institute.

Condition or disease
Prostate Cancer

Detailed Description:

OBJECTIVES: Major innovations in radiotherapy (RT) delivery (3D conformal RT, intensity modulated RT) now permit RT dose escalation to be tested as a means of improving control of localized prostate cancer. With delivery innovations, severe toxicity occurs rarely, but significant bladder and rectal toxicity is common. The investigators have studied a cohort of 98 patients who received dose-escalated 3D-CRT and have obtained evidence of dosimetric factors underlying rectal toxicity. They posit that the late radiation toxicity disease state has significant genetic determinants. These determinants are neither understood nor accounted for in selection of treatment, and the investigators propose to study the above well-characterized cohort, who are clinically well from a disease control perspective, given that comprehensive dosimetric and outcome information is available on all.

HYPOTHESIS: Comprehensive analysis of the genomic, proteomic, and dosimetric characteristics of patients with prostate cancer will provide a novel understanding of the genetic predisposition of cellular and tissue responses to irradiation which result in the clinical occurrence of significant chronic rectal and bladder injury after 3D-CRT.

APPROACH: For a thorough understanding of the molecular processes underlying tissue responses to radiation damage, the investigators propose a genomic analysis. Their working hypothesis is that rectal and bladder toxicity will be correlated to patient genetics as measured by single nucleotide polymorphisms (SNPs) in a select group of genes. The criteria for selecting SNPs will be based on evidence for the various genes implicated or demonstrated in DNA repair pathways and radiation-induced tissue damage. In addition, since radiation injury can be considered a phenotypic tissue response to RT in genetically predisposed individuals, the investigators will examine the protein profile "signature" in sera from patients who have suffered significant toxicity. Analysis of these data will be unique in that the investigators will use both statistically based bioinformatics approaches, and biophysical modeling. This proposal represents the most comprehensive exploration to date of the concept of a molecular "signature" of normal tissue radiation injury of which the applicants are aware.


  • To create a database of SNPs among long-term prostate cancer survivors who have been treated with 3D-CRT, and for whom detailed toxicity, quality of life and dosimetric information are available;
  • To assess the feasibility of using bioinformatics approaches with this database to examine the possibility that specific SNPs, in the context of known dosimetric factors, can predict occurrence of late rectal or bladder toxicity;
  • To perform a proteomic analysis of serum samples from a cohort of 25 patients experiencing higher levels of ongoing late toxicity and 50 patients with no ongoing late toxicity.


  • To utilize biophysical approaches to modelling clinical complication data, using the concept of generalized mean biological effective dose (GMBED) and the critical volume model.

SUMMARY: This proposal will be the first comprehensive retrospective analysis of genomic, proteomic and dosimetric determinants of late radiation injury in prostate cancer. The investigators have assembled a broad array of expertise from the CCI PolyomX program (the only high throughput SNP facility in western Canada), the NCI/FDA Clinical Proteomics Program at Bethesda, MD, and the unique biophysical modeling capability of CBIAR researchers to reach these goals.

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Study Type : Observational
Actual Enrollment : 83 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Exploring Genomic, Proteomic and Dosimetric Determinants of Late Toxicity After Three Dimensional Conformal RT for Prostate Cancer
Study Start Date : April 2003
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
community sample

Inclusion Criteria:

  • Treatment with 3D CRT for which follow-up toxicity evaluation was done

Exclusion Criteria:

  • Follow-up less than 18 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00122265

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Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Sponsors and Collaborators
AHS Cancer Control Alberta
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Principal Investigator: Matthew Parliament, MD Cross Cancer Institute
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Responsible Party: AHS Cancer Control Alberta Identifier: NCT00122265    
Other Study ID Numbers: GU-6-0035/ethics 17075
First Posted: July 22, 2005    Key Record Dates
Last Update Posted: February 26, 2016
Last Verified: April 2012
Keywords provided by AHS Cancer Control Alberta:
prostate cancer
radiation toxicity
single nucleotide polymorphism
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases