Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast
- Conditions
- Carcinoma, Ductal, Breast
- Interventions
- Radiation: Shorter WB fractionation + BoostRadiation: Shorter WB fractionationRadiation: Standard WB fractionation+BoostRadiation: Standard WB fractionation
- 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
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.
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
- Arm && Interventions
Group Intervention Description Arm 4 (Shorter WB fractionation + Boost) Shorter WB fractionation + Boost Whole breast RT + tumour bed boost - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days; Boost 16 Gy/8 fractions/10 days) Arm 2 (Shorter WB Fractionation) Shorter WB fractionation Whole Breast RT alone - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days) Arm 3 (Standard WB fractionation+Boost) Standard WB fractionation+Boost Whole Breast RT + tumor bed boost - Standard fractionation schedule (50 Gy/25 fractions/35 days; Boost 16 Gy/8 fractions/10 days) Arm 1 (Standard WB Fractionation) Standard WB fractionation Whole Breast RT alone - Standard fractionation schedule (50GY/25 Fractions/35days)
- Primary Outcome Measures
Name Time Method 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
Name Time Method Quality of Life change Assessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT. Time to disease recurrence Measured 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 Outcome Cosmetic assessment will take place at baseline, 12, 36 and 60 months post RT. Radiation toxicity Assessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10. Overall survival Measured 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)
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Algemeen Ziekenhis Sint-Augustinus
🇧🇪Wilrijk, Belgium
ISALA Klinieken
🇳🇱Zwolle, Netherlands
Musgrove Park Hospital
🇬🇧Taunton, Somerset, United Kingdom
Onze Lieve Vrouw Ziekenhuis
🇧🇪Aalst, Belgium
Launceston General Hospital
🇦🇺Launceston, Tasmania, Australia
Universitair Zielenhusi
🇧🇪Brussel, Belgium
Barwon Health - Andrew Love Cancer Care Centre, Geelong Hospital
🇦🇺Geelong, Victoria, Australia
AZ Groeninghe - Campus Maria's Voorzienigheid
🇧🇪Kortrijk, Belgium
Arnhem 'S Radiotherapeutisch Instituut
🇳🇱Arnhem, Netherlands
University of North Staffordshire
🇬🇧Stoke-On-Trent, Staffordshire, United Kingdom
Campbelltown Hospital
🇦🇺Campbelltown, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Nepean Cancer Care Centre
🇦🇺Kingswood, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Riverina Cancer Care Centre
🇦🇺Wagga Wagga, New South Wales, Australia
Premion - Wesley
🇦🇺Auchenflower, Queensland, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Radiation Oncology - Mater Centre
🇦🇺South Brisbane, Queensland, Australia
Toowoomba Cancer Research Centre
🇦🇺Toowoomba, Queensland, Australia
Genesis Cancer Care (previously Premion) - Tugun
🇦🇺Tugun, Queensland, Australia
North Queensland Oncology Service
🇦🇺Townsville, Queensland, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Austin Hospital
🇦🇺Melbourne, Victoria, Australia
William Buckland Radiotherapy Centre, Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Sir Charles Gardiner Hospital
🇦🇺Nedlands, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Perth Radiation Oncology
🇦🇺Perth, Western Australia, Australia
Cliniques Univeritaires St Luc
🇧🇪Brussel, Belgium
Hopital De Jolimont
🇧🇪Haine St Paul, Belgium
Nova Scotia Cancer Centre
🇨🇦Halifax, Canada
Jurvanski Cancer Centre
🇨🇦Hamilton, Canada
Notre Dame Hospital
🇨🇦Hearst, Canada
London Regional Cancer Program
🇨🇦London, Canada
Hospital Maisonneuve-Rosemont
🇨🇦Montreal, Canada
BCCA Southern Interior - CAVK
🇨🇦Kelowna, Canada
Leon Richard Oncology Centre
🇨🇦Moncton, Canada
CHUQ L'Hotel-Dieu de Quebec
🇨🇦Quebec, Canada
McGill University Department of Oncology
🇨🇦Sainte-Anne-de-Bellevue, Canada
Allan Blair Cancer Centre
🇨🇦Saskatoon, Canada
Lakeridge Health
🇨🇦Oshawa, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Canada
Odette Cancer Centre
🇨🇦Toronto, Canada
Universite de Sherbrooke - CUGH
🇨🇦Sherbrooke, Canada
Thunder Bay Regional Health Sciences Centre
🇨🇦Thunder Bay, Canada
BCCA Vancouver Centre
🇨🇦Victoria, Canada
Princess Margaret Hospital
🇨🇦Toronto, Canada
Vancouver Island Cancer Centre
🇨🇦Victoria, Canada
Chr De Grenoble - La Tronche
🇫🇷Grenoble, France
Cancer Care Manitoba
🇨🇦Winnipeg, Canada
Centre Antine Lacassagne
🇫🇷Nice, France
University Hospital Galway
🇮🇪Galway, Ireland
SLRON (St Luke's Rad Onc Network)
🇮🇪Rathgar, Ireland
Centro Di Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
Fondazione Salvatore Maugeri
🇮🇹Pavia, Italy
Cancer Institute Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Academisch Medisch Centrum
🇳🇱Amsterdam,, Netherlands
Reinier de Graaf Groep
🇳🇱Delft, Netherlands
Leiden University Medical Centre
🇳🇱Leiden, Netherlands
Maastricht Radiation Oncology Maastro Clinic
🇳🇱Maastricht, Netherlands
University Medical Centre Groningen
🇳🇱Groningen, Netherlands
Medisch Centrum Haaglanden
🇳🇱Westeinde, Netherlands
Auckland Hospital
🇳🇿Auckland, New Zealand
National University Hospital
🇸🇬Singapore, Singapore
Waikato Hospital
🇳🇿Hamilton, New Zealand
IOSI
🇨🇭Bellinzona, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
University Hospital Basel
🇨🇭Basel, Switzerland
Kantonsspital Graubunden
🇨🇭Chur, Switzerland
Inselspital Bern
🇨🇭Bern, Switzerland
Kantonsspital Munsterlingen
🇨🇭Munsterlingen, Switzerland
Gloucestershire Royal & Cheltenham General Hospitals
🇬🇧Cheltenham, Gloucestershire, United Kingdom
Brust-Zentrum Zurich-Seefeld
🇨🇭Zurich, Switzerland
Klinik Hirslanden
🇨🇭Zurich, Switzerland
Ealing Hospital
🇬🇧Southall, Middlesex, United Kingdom
Mount Vernon Cancer Centre
🇬🇧Northwood, Middlesex, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Basildon University Hospital
🇬🇧Basildon, United Kingdom
Queens Hospital Burton
🇬🇧Burton-On-Trent, Staffordshire, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Sandwell and West Birmingham Hospitals NHS Trust
🇬🇧Birmingham, United Kingdom
Bristol Haematology & Oncology
🇬🇧Bristol, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Coventry Arden Cancer Centre
🇬🇧Coventry, United Kingdom
Colchester Hospital
🇬🇧Colchester, United Kingdom
Dumfries & Galloway Royal Infirmary
🇬🇧Dumfries, United Kingdom
Queen Margaret Hospital
🇬🇧Dunfermline, United Kingdom
Edinburgh Western General Hospital
🇬🇧Edinburgh, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
Kidderminster Hospital
🇬🇧Kidderminster, United Kingdom
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Nottingham University Hospitals
🇬🇧Nottingham, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
James Cook University Hospital
🇬🇧Middlesborough, United Kingdom
Stafford Hospital
🇬🇧Stafford, United Kingdom
Royal Marsden
🇬🇧Sutton, United Kingdom
Alexandra Hospital
🇬🇧Redditch, United Kingdom
Southend University Hopstial
🇬🇧Southend, United Kingdom
Warwick Hospital
🇬🇧Warwick, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Westmead Hospital
🇦🇺Wentworthville, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Genesis Cancer Care (previously Premion) - Nambour
🇦🇺Nambour, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Saint John Regional Hospital
🇨🇦Miramichi, Canada
Cork University Hospital
🇮🇪Cork, Ireland
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Churchill Hospital
🇬🇧Oxford, Headington, United Kingdom
Pilgram Hospital
🇬🇧Boston, Lincolnshire, United Kingdom
Kings Mill Hospital Nottingham
🇬🇧Sutton-In-Ashfield, Nottinghamshire, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, United Kingdom
Imperial College Healthcare Charing Cross
🇬🇧London, United Kingdom
Royal Alexandra Hospital
🇬🇧Paisley, United Kingdom
The Shrewsbury and Telford Hospital NHS Trust
🇬🇧Shrewsbury, United Kingdom