An International Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy Boost With Conventional External Beam Radiotherapy Boost After Lumpectomy for Breast Cancer in Women With a High Risk of Local Recurrence.
N/A
N/A
Female
Early Breast Cancer
Trial Information
An International Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy Boost With Conventional External Beam Radiotherapy Boost After Lumpectomy for Breast Cancer in Women With a High Risk of Local Recurrence.
DESIGN: A pragmatic multi-centre randomised clinical trial to test whether TARGeted
Intraoperative radioTherapy as a tumour bed Boost (TARGIT-B) is superior in terms of local
relapse within the treated breast compared with standard post-operative external beam
radiotherapy boost in women undergoing breast conserving therapy who have a higher risk of
local recurrence. Patients can be entered before the primary surgery or in a smaller
proportion of cases, post-pathology. SETTING: Specialist breast units in UK, USA, Canada,
Australia and Europe; 31 centres currently recruiting in the TARGIT-A trial and several are
ready to join. TARGET POPULATION: Breast cancer patients suitable for breast conserving
surgery, but with a high risk of local recurrence. Details of inclusion and exclusion are
given in part 2. Briefly the patients should be either younger than 45 or if older, need to
have certain pathological features that confer a high risk of local recurrence of breast
cancer. HEALTH TECHNOLOGIES BEING ASSESSED. The TARGIT Technique: The Intrabeam® (Carl
Zeiss, FDA approved and CE marked) is a miniature electron beam-driven source which provides
a point source of low energy X-rays (50kV maximum) at the tip of a 3.2mm diameter tube. The
radiation source is inserted into the tumour bed immediately after excision of the tumour
and switched on for 20-35 minutes to provide intra-operative radiotherapy accurately
targeted to the tissues that are at highest risk of local recurrence. The physics, dosimetry
and early clinical applications of this soft x-ray device have been well studied. For use in
the breast, the technique was first developed and piloted at University College London. The
radiation source is surrounded by a spherical applicator, specially designed (and available
in various sizes) to produce a uniform field of radiation at its surface, enabling delivery
of an accurately calculated dose to a prescribed depth. It is inserted in the tumour bed and
apposed to it with surgical sutures and/or other means. As the x-rays rapidly attenuate the
dose to more distant tissues is reduced; this also allows it to be used in standard
operating theatres. 20 Gy is delivered to the tumour bed surface in 20-35 minutes, after
which the radiation is switched off, the applicator removed, and the wound closed in the
normal way. This simple technique has potentially several advantages over convential
external beam radiotherapy, interstitial implantation of radioactive wires or conformal
external beam radiotherapy. The first pilot of twenty-five cases was at performed at UCL
using TARGIT technique as a replacement for the boost dose of radiotherapy; full dose
external beam treatment was subsequently given. The phase II study of 300 patients was
published and recently updated with long term data along with favourable toxicity and
cosmetic outcome results of individual cohorts. A mathematical model of TARGIT developed
recently (funded by Cancer Research UK) suggests that it could be superior to conventional
radiotherapy. Translational research has found that TARGIT impairs the
surgical-trauma-stimulated proliferation and invasiveness of breast cancer cells. This
effect of radiotherapy may act synergistically with its tumouricidal effect yielding a
superior result. MEASUREMENT OF COST AND OUTCOME: Patient assessments will be clinical
examination (6 monthly x 3 years then yearly x 10 years) and mammography (yearly). with
ulstrasound (if needed) . Primary outcome: histologically/cytologically proven local
recurrence. Secondary: site of relapse in the breast, overall survival, local toxicity (RTOG
and LENT SOMA criteria), cosmesis, quality of life, patient satisfaction and health
economics. The cost and cost-effectiveness of TARGIT versus EBRT, both as boost, will be
calculated from a NHS and personal social services (PSS) perspective. Costs directly
incurred by patients will also be assesed, since EBRT as a boost is likely to impose
additional time and travel expense to patients and families.
Inclusion Criteria:
At least one of these criteria must be satisfied:
1. Less than 46 years of age
2. More than 45 years of age, but with one of the following poor prognostic factors:
1. lymphovascular invasion
2. gross nodal involvement (not micrometastasis)
3. more than one tumour in the breast but still suitable for breast conserving
surgery through a single specimen
3. More than 45 years of age, but with at least two of the following poor prognostic
factors
1. ER and/or PgR negative
2. Grade 3 histology
3. Positive margins at first excision
4. Those patients with large tumours which have responded to neo-adjuvant chemo- or
hormone therapy in an attempt to shrink the tumour and are suitable for breast
conserving surgery as a result.
5. Lobular carcinoma or Extensive Intraductal Component (EIC)
6. A list (one to many) of high risk factors are present (as predefined in the policy
document) that give a high risk of local recurrence.
7. Patients with either HER2 positive or HER2 negative can be included.
Exclusion Criteria:
1. Bilateral breast cancer at the time of diagnosis.
2. Patients with any severe concomitant disease that may limit their life expectancy
3. Previous history of malignant disease does not preclude entry if the expectation of
relapse-free survival at 10 years is 90% or greater (e.g., non-melanoma skin cancer,
CIN, etc).
4. No more than 30 days can have elapsed between last breast cancer surgery (not
axillary) and randomisation for patients in the post-pathology stratification unless
part of a specific clinical trial that addresses the question of timing or tumour bed
can be reliably identified, e.g., by ultrasound.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Local tumour control (defined as no recurrent tumour in the ipsilateral breast).
Outcome Description:
To evaluate whether a tumour bed boost in the form of a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is superior (in terms of local tumour control) to standard post-operative external beam radiotherapy boost, after breast conserving surgery in women undergoing breast conserving therapy who have a higher risk of local recurrence.
Outcome Time Frame:
Five year median follow-up
Safety Issue:
No
Principal Investigator
Jayant S Vaidya, MBBS FRCS
Investigator Role:
Principal Investigator
Investigator Affiliation:
University College, London
Authority:
United Kingdom: Research Ethics Committee
Study ID:
TARGIT Boost
NCT ID:
NCT01792726
Start Date:
March 2013
Completion Date:
April 2022
Related Keywords:
- Early Breast Cancer
- breast cancer
- radiotherapy
- TARGIT
- Intrabeam
- Breast Neoplasms
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