“The most important benefit of TARGIT for a woman with breast cancer is that it allows her to complete her entire local treatment [lumpectomy and radiation therapy] at the time of her operation, with lower toxicity.”
- The TARGIT technique uses the Intrabeam device for delivering precise and timely dose of intraoperative radiotherapy accurately to the tumour bed.
- An academic insight led to the development of this device through a collaborative effort between University College London and the Photoelectron Corporation in 1990s.
- It was first used on 2 July 1998 in the Middlesex Hospital, UCL, London. Intrabeam is currently manufactured by Carl Zeiss
What was done in the TARGIT-A trial?
- The TARGIT-A trial was a randomised trial testing an individualised approach of radiation after lumpectomy for breast cancer.
- The comparison in the TARGIT-A trial was between standard radiation therapy that is given over several weeks after a lumpectomy vs. a risk-adapted approach using single dose of TARGeted Intraoperative radioTherapy (TARGIT) given at the time of lumpectomy.
- The risk-adapted protocol recommended that if the patients who had received TARGIT were found to have high risk factors postoperatively, they also received whole breast radiation – which occurred in 15-20% of cases as expected in the protocol; otherwise, about 80% of such patients completed their treatment (surgery and radiation) during their lumpectomy.
- The pre-specified non-inferiority margin was an absolute difference in local recurrence of breast cancer between TARGIT and EBRT of 2.5% — in simple terms, if the absolute difference in local recurrence between the two treatments being compared was less than 2.5%, they would be considered non-inferior to each other in terms of local control of breast cancer. Patient preference studies have suggests majority of patients consider such a 2.5% margin as appropriate.
- 3451 patients from 33 centres in 11 countries participated in the TARGIT-A trial (UK, USA, Germany, Italy, France Poland , Switzerland, Norway, Denmark, Canada and Australia) from 24 March 2000 to 25 June 2012. (map).
TARGIT-A Trial Design
In the randomised TARGIT-A trial, two policies of local radiation treatment are compared:
Eligible patients were recruited at either of the two stages of their treatment in the pragmatic Targit trial:
Before the primary surgery (Prepathology randomisation)
This is the original method of entry into the TARGIT-A trial for a breast cancer patient. Once the decision to do a wide local excision (lumpectomy) is taken, and informed consent obtained, the randomisation takes place before surgery and if randomised to TARGIT, it is delivered to the fresh tumour bed immediately after lumpectomy for breast cancer. If at the postoperative pathology review, it is felt that they have a particularly high risk of local recurrence especially in other quadrants ( EIC, invasive lobular carcinoma or positive excision margins) then external beam radiotherapy can be added- all as part of the experimental arm of the trial. Centres could pre-specify additional such factors such as extensive lymphovascular invasion, multiple positive nodes, etc.
After the primary surgery (Postpathology randomisation)
This mode of entry into the trial was added to enable patients in whom the excision of the cancer had already been performed. This was logistically easier in some centres and theoretically allowed better case selection – although it required a second procedure to be performed. Randomisation in the Targit-A trial is performed after the the primary cancer is removed and if allocated to receive TARGIT, single session intraoperative radiotherapy is given as a day-case operation .
What was found? Results of the TARGIT-A trial
- When TARGIT is given with lumpectomy, the 5-year local recurrence of breast cancer is similar to EBRT
- When TARGIT is given as a second procedure, the difference in local recurrence between TARGIT and EBRT was more than 2.5%
- Breast cancer mortality with TARGIT were similar to EBRT
- Mortality from other causes was significantly lower with TARGIT due to fewer deaths from cardiovascular causes and other cancers.
- The results remain stable with longer follow up. The results were the same for the large number (1222) patients who were treated between 2000-2008 and had a median follow up of 5 years.
Is the follow up of the TARGIT-A trial long enough?
- Although breast cancer can continue to recur beyond 5 years, the peak hazard is in the first 2-3 years. More importantly, the beneficial effect of radiotherapy on local recurrence is mostly in the first 2-3 years with no further benefit beyond the first 5 years after surgery.
- Thus, for local recurrence in radiotherapy trials, the 5-year results are indicative of longer term results.
- The TARGIT-A trial has a large number of patients (n=1222) with a median follow up of 5 years and even larger 2232 with a median follow up of nearly 4 years.
- Therefore, these results can be relied upon to guide the application of TARGIT using Intrabeam in routine clinical practice in appropriate patients. For a more detailed explanation see Why is the follow up duration in TARGIT-A trial adequate?. PDF
TARGIT IORT for breast cancer vs. several weeks of radiotherapy
A robust response to some scientifically weak criticism- along with new figures: Pride, Prejudice or Science- attitudes towards the results of the TARGIT-A trial of targeted intraoperative radiotherapy for breast cancer. Click for full text PDF
The TARGIT trial office has received its main funding from the Health Technology Assessment programme of the National Institutes of Health Research, Department of Health, UK for the TARGIT-A and TARGIT-B trials
First publication of the main results:
Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. The Lancet. 2010 ;376(9735):91-102.
5-year results and first analysis of survival
Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sütterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HMR, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. The Lancet. 11 November 2013. doi:10.1016/s0140-6736(13)61950-9 Full text PDF Podcast