Study of DNA Mutations in Predicting the Effect of External-Beam Radiation Therapy in Patients With Early Breast Cancer, Localized Prostate Cancer, or Gynecological Cancer

The Christie NHS Foundation Trust

Status: Unknown

Conditions: Endometrial Cancer; Breast Cancer; Sarcoma; Vulvar Cancer; Primary Peritoneal Cavity Cancer; Vaginal Cancer; Fallopian Tube Cancer; Ovarian Cancer; Prostate Cancer; Cervical Cancer

Treatments: Other: laboratory biomarker analysis; Genetic: polymorphism analysis; Genetic: gene expression analysis; Genetic: gene rearrangement analysis; Radiation: radiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00601406

CDR0000581139

CHNT-RAPPER

EU-20798

Details and patient eligibility

About

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This clinical trial is evaluating DNA mutations in predicting the effect of external-beam radiation therapy in patients with early breast cancer, localized prostate cancer, or gynecologic cancer.

Full description

OBJECTIVES:

Primary

• To test the hypothesis that an association between common genetic variations, reported by single nucleotide polymorphisms (SNP) in relevant candidate genes, is associated with individual patient variability in normal tissue radiation response and toxicity.

Secondary

• To compare different clinical scoring systems for late normal tissue effects, specifically Late Effect of Normal Tissue Subjective Objective Management Analysis (LENT SOMA), Radiation Therapy Oncology Group (RTOG), quality of life, and in a subset common terminology criteria (CTC) version 3.
• To compare clinical scoring systems with analytical measures of normal tissue outcome in a minority of patients, using volume change in the breast measured by laser camera.
• To correlate family history information with SNP analysis to produce a polymorphism risk score (PRS) for family history.
• To compare a detailed 3D dose-volume analysis in a subset of patients with late effects and SNP results.
• To correlate actuarial analysis of late effects changes over time with PRS.
• To conduct PRS analyses against tumor control probability (TCP), using survival as a surrogate for TCP where necessary, and normal tissue complications vs tumor control probability.

OUTLINE: This is a multicenter study.

Patients are recruited from clinical trials in which their late normal tissue effects have been measured. Blood samples are collected from these patients for analysis of genetic variation by DNA extraction and single nucleotide polymorphism analysis. Sixty different genes, including those involved in cell cycle checkpoint control, DNA damage recognition and repair, induction of apoptosis, and cytokine production (including TGFβ pathways) are assessed.

Enrollment: 2,200 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Patients must have received curative external-beam radiotherapy within the context of a formal clinical study for any of the following:

  • Early breast cancer after breast-conserving surgery
  • Localized prostate cancer
  • Gynecological cancer (may have also received brachytherapy)

• Venous blood samples must be available

• Patients will be identified from the following clinical studies:

  • Cambridge intensity-modulated radiotherapy breast randomized trial
  • RT01 prostate radiotherapy randomized trial/other prostate trials
  • Christie hospital breast, prostate, and gynecological cancer radiotherapy patients

• Must have minimum follow up with late normal tissue effect scoring for two years available

PATIENT CHARACTERISTICS:

• No other malignancy prior to treatment for the specified tumor types except basal cell or squamous cell carcinoma of the skin or in situ carcinoma

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics