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Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast

Not Applicable
Active, not recruiting
Conditions
Carcinoma, Ductal, Breast
Registration Number
NCT00470236
Lead Sponsor
Trans Tasman Radiation Oncology Group
Brief Summary

Hypotheses:

1. The addition of tumour bed boost after BCS in women with non-low risk DCIS reduces the risk of local recurrence (invasive or intraductal recurrence in the ipsilateral breast).

2. The risk of local recurrence in the shorter fractionation arm is not worse than that for the standard fractionation arm.

3. A molecular signature predictive of invasive recurrence of DCIS will be detectable and the molecular signature may eventually have clinical utility for therapy individualization.

Overall Objectives:

1. To improve the outcome of women with non-low risk DCIS treated with breast conserving therapy.

2. To individualize treatment selection for women with DCIS to achieve long term disease control with minimal toxicity.

Detailed Description

Specific objectives:

1. To evaluate time to local recurrence in women with DCIS treated with breast conserving surgery followed by:

* whole breast RT alone versus whole breast RT plus tumour bed boost;

* RT using the standard fractionation schedule versus the shorter schedule.

2. To evaluate time to disease recurrence and overall survival in women with DCIS treated with breast conserving surgery followed by:

* whole breast RT alone versus whole breast RT plus tumour bed boost;

* RT using the standard fractionation schedule versus the shorter schedule.

3. To compare the toxicity of:

* whole breast RT alone versus whole breast RT plus tumour bed boost;

* RT using the standard fractionation schedule versus the shorter schedule.

4. To compare the cosmetic outcome of:

* whole breast RT alone versus whole breast RT plus tumour bed boost;

* RT using the standard fractionation schedule versus the shorter schedule.

5. To identify a molecular signature predictive of invasive recurrence of DCIS to facilitate therapy individualization.

6. To assess inter-relationship of biomarkers and relationship between biomarker expression and specific histopathologic features of DCIS.

7. To evaluate the quality of life of women treated with:

* whole breast RT alone versus whole breast RT plus tumour bed boost;

* RT using the standard fractionation schedule versus the shorter schedule.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
1608
Inclusion Criteria

Patients must fulfill all of the following criteria for admission to study:

  • Women ≥ 18 years.

  • Histologically proven DCIS of the breast without an invasive component.

  • Bilateral mammograms performed within 6 months prior to randomization.

  • Clinically node-negative.

  • Treated by breast conserving surgery (primary excision or re-excision) with complete microscopic excision and clear radial margins of ≥1 mm* (*Patients with superficial or deep resection margin of <1 mm are eligible if surgery has removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia).

  • Women who are at high risk of local recurrence due to:

    • Age < 50 years; OR

    • Age ≥ 50 years plus at least one of the following:

      • Symptomatic presentation
      • Palpable tumour
      • Multifocal disease
      • Microscopic tumour size ≥ 1.5 cm in maximum dimension
      • Intermediate or high nuclear grade
      • Central necrosis
      • Comedo histology
      • Radial* surgical resection margin < 10 mm. (*Patients with superficial or deep resection margin of < 10 mm are eligible if surgery has not removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia.)
  • Assessed by surgeon and radiation oncologist to be suitable for breast conserving therapy including whole breast RT.

  • Ability to tolerate protocol treatment.

  • Protocol RT should preferably commence within 8 weeks but must commence no later than 12 weeks from the last surgical procedure.

  • ECOG performance status 0, 1 or 2.

  • Patient's life expectancy > 5 years.

  • Availability for long-term follow-up.

  • Written informed consent.

Exclusion Criteria

Patients who fulfill any of the following criteria are not eligible for admission to study:

  • Multicentric disease or extensive microcalcifications that could not be completely excised by breast conserving surgery with radial margins of ≥1 mm*.

    *Patients with superficial and/or deep margin of <1 mm are eligible if surgery has removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia.

  • Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical examination (if lymph node biopsy or dissection has been performed).

  • Locally recurrent breast cancer.

  • Previous DCIS or invasive cancer of the contralateral breast.

    • Bilateral DCIS of the breasts
    • Synchronous invasive carcinoma of the contralateral breast
  • Other concurrent or previous malignancies except:

    • Non-melanomatous skin cancer;
    • Carcinoma in situ of the cervix or endometrium; and
    • Invasive carcinoma of the cervix, endometrium, colon, thyroid and melanoma treated at least five years prior to study admission without disease recurrence.
  • Serious non-malignant disease that precludes definitive surgical or radiation treatment (e.g., scleroderma, systemic lupus erythematosus, cardiovascular/pulmonary/renal disease).

  • ECOG performance status ≥ 3.

  • Women who are pregnant or lactating.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Time to local recurrence, measured from the date of randomization to the date of first evidence of local recurrence.Main analysis after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Secondary Outcome Measures
NameTimeMethod
Quality of Life changeAssessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT.
Time to disease recurrenceMeasured from the date of randomization to the date of first evidence of recurrent disease. Main analysis of secondary outcomes after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Cosmetic OutcomeCosmetic assessment will take place at baseline, 12, 36 and 60 months post RT.
Radiation toxicityAssessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10.
Overall survivalMeasured from the date of randomization to the date of death from any cause. Main analysis of secondary outcomes after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.

Trial Locations

Locations (120)

Campbelltown Hospital

🇦🇺

Campbelltown, New South Wales, Australia

Nepean Cancer Care Centre

🇦🇺

Kingswood, New South Wales, Australia

St George Hospital

🇦🇺

Kogarah, New South Wales, Australia

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Royal North Shore Hospital

🇦🇺

St Leonards, New South Wales, Australia

Riverina Cancer Care Centre

🇦🇺

Wagga Wagga, New South Wales, Australia

Calvary Mater Newcastle

🇦🇺

Waratah, New South Wales, Australia

Westmead Hospital

🇦🇺

Wentworthville, New South Wales, Australia

Premion - Wesley

🇦🇺

Auchenflower, Queensland, Australia

Royal Brisbane and Women's Hospital

🇦🇺

Brisbane, Queensland, Australia

Scroll for more (110 remaining)
Campbelltown Hospital
🇦🇺Campbelltown, New South Wales, Australia

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