TARGIT - IORT

Why is radiotherapy used for breast cancer?

Breast cancer is frequently treated by surgically removing the cancerous lump with a margin of surrounding normal tissue. Radiotherapy to the remaining breast after such a lumpectomy reduces the risk of cancer coming back in the breast. Traditional external beam radiotherapy (EBRT) is given to the whole breast a few weeks after surgical removal of the cancer. As it is not focused, it needs to be given in daily small doses over three to six weeks.

What is Intraoperative radiotherapy | Intrabeam | TARGIT | IORT for breast cancer?

TARGIT IORT stands for TARGeted Intraoperative radioTherapy. It is given during a lumpectomy for breast cancer, under the same anaesthetic, and it can replace traditional radiotherapy in suitable patients. The TARGIT technique and the Intrabeam device was developed by clinical academics at University College London in 1998 in collaboration with the manufacturers. After a cancer has been removed from the breast, TARGIT IORT allows your doctor to deliver a dose of radiotherapy directly into your breast, focussed to the site where the tumour had been. A small ball-shaped radiation applicator of the Intrabeam device is precisely placed in the tumour bed – the cavity left behind when the tumour is removed. TARGIT IORT is given over about 25 minutes, the applicator then is removed and skin closed. Intrabeam TARGIT intraoperative radiotherapy effectively treats the tissues where cancer might have come back while avoiding radiation to the skin and other healthy tissues such as the heart and lungs This method has been used worldwide (over 300 centres in 38 countries) to treat over 40,000 patients.

What is the surgical procedure of giving TARGIT IORT?

TARGIT IORT is given using the Intrabeam device. It is given during your surgery, while you remain asleep, under general anaesthetic. It adds about 30 minutes to the operation. It allows your specialist to deliver a focused dose of radiotherapy into the space where the breast cancer had been. This means that the radiotherapy is accurately targeted within the breast. This method avoids the potential damage to the skin, heart and lungs from traditional radiotherapy. You do not feel any effects from the radiotherapy and there are no additional scars on your breast. The surgical technique of Intrabeam TARGIT IORT, simplified: The surgeon removes the cancerous lump from the breast. The cancer and some surrounding normal tissue - the margin - is removed, leaving a small space called the tumour bed. A ball-shaped radiation small applicator is positioned precisely within the breast cavity, at the site of tumour, using meticulously placed sutures. Intrabeam TARGIT IORT is given as focused dose of targeted intraoperative radiotherapy into the breast, avoiding damage to the skin, heart and lungs.This takes about 30 minutes The breast wound and skin is surgically closed as usual.

Has TARGIT IORT been clinically tested for breast cancer?

TARGIT IORT has been extensively tested in clinical trials over the past 20 years. The TARGIT-A trial, included 3451 patients treated in 33 hospitals in UK, Europe, USA and Australia and this trial compared TARGIT IORT with traditional radiotherapy. TARGIT IORT is given using the Intrabeam device. TARGIT IORT avoids radiation to the whole breast. It is given from within the breast, so the skin is protected. Therefore, it has only minimal side effects. Clinical trial results show that radiation treatment side effects are fewer compared with traditional radiotherapy and the cosmetic outcome is similar to or better. The five-year results showed that when TARGIT is given at the same time as lumpectomy, the local-recurrence-free-survival is similar to traditional radiotherapy: 93.9% with TARGIT vs. 92.5% with traditional EBRT. As with all breast cancer treatments there is some uncertainty about the exact difference in local recurrence after TARGIT IORT compared with traditional radiotherapy. However, the UK National Institute of Care and Excellence have determined that such difference is very small (1 to 2%) and have recommended it for suitable patients in the NHS.

What will it involve?

You will have your surgery the usual way and TARGIT IORT will be given using the Intrabeam device during the operation, under the same anaesthetic. Afterwards you will be able to go home on the same day or after an overnight stay. The wound care is similar to a standard operation, but the sutures or ‘Steristrips’ need to be left for 14 days. Compared with traditional treatment, there is a lower risk of skin injury, but a slightly (1%) higher chance of fluid collecting in the wound. This does not delay the healing process. Sometimes, in 15-20% of women, additional information from analysis of the cancer after surgery may mean that a smaller course of traditional EBRT required after TARGIT.

Who can and cannot have TARGIT IORT?

Women who are 45 or older with invasive ductal type cancer suitable for breast conservation (tumour size up to 3.5cm) are eligible to receive TARGIT IORT instead of EBRT. Other women who have a higher risk cancer can receive TARGIT as a tumour-bed boost in addition to EBRT within the TARGIT-B trial. Women who need a mastectomy are not suitable.

Key Benefits of Intrabeam TARGIT IORT

Takes less time: TARGIT IORT is given during your surgery rather than after a few weeks' delay before a three or four week course of daily doses of traditional radiotherapy. Precise radiotherapy: The radiotherapy is given into the breast exactly where the cancer had been, ensuring that it is accurately delivered. Protects health tissues: There is reduced toxicity or damage to the skin, heart or lungs. Avoids delay: Radiotherapy does not need to be delayed until after chemotherapy. Flexible for your needs: Intrabeam TARGIT IORT can be supplemented with whole breast radiotherapy if it is thought necessary later on ​ Quality of life and cosmetic results: are as good or better than traditional radiotherapy

Key Concerns about Intrabeam TARGIT IORT

Possible need for further radiotherapy: About 15-20% of patients may need to receive traditional radiotherapy in addition to TARGIT IORT if it is felt necessary after detailed microscopic examination of the tumour after surgery. The safety of TARGIT IORT is well established with 5-year median follow available for 1222 patients. With longer follow up, local recurrence with TARGIT may be 1% - 2% higher than traditional radiotherapy. This does not reduce survival; in fact, there are fewer deaths with targeted radiation compared with whole breast radiation. See http://goo.gl/ptc6L9 This pictogram is made by applying the 5-year results of the TARGIT-A trial to 2000 women, to help patients and doctors to make a shared well-informed decision about TARGIT IORT ​​

NICE Recommendation

In February 2017 NICE issued a press release stating that they have recommended the use of TARGIT IORT in the treatment women with early breast cancer. https://twitter.com/NICEcomms/status/831850566741471233 ​ NICE issued their final guidance on 31 January 2018 https://www.nice.org.uk/guidance/ta501 ​ Click here for a printable information to help in a shared decision making that has been prepared by TARGIT IORT specialists in collaboration with patients.

How was TARGIT IORT for breast cancer developed?

• The TARGIT technique uses the Intrabeam device for delivering precise and timely dose of intraoperative radiotherapy accurately to the tumour bed.

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.

How is TARGIT IORT given during surgery?

TARGIT IORT is given using the Intrabeam device. It is given during your surgery, while you remain asleep, under general anaesthetic. It adds about 30 minutes to the operation. It allows your specialist to deliver a focused dose of radiotherapy into the space where the breast cancer had been. This means that the radiotherapy is accurately targeted within the breast. This method avoids the potential damage to the skin, heart and lungs from traditional radiotherapy. You do not feel any effects from the radiotherapy and there are no additional scars on your breast. The surgical technique of Intrabeam TARGIT IORT, simplified: The surgeon removes the cancerous lump from the breast. The cancer and some surrounding normal tissue - the margin - is removed, leaving a small space called the tumour bed. A ball-shaped radiation small applicator is positioned precisely within the breast cavity, at the site of tumour, using meticulously placed sutures. Intrabeam TARGIT IORT is given as focused dose of targeted intraoperative radiotherapy into the breast, avoiding damage to the skin, heart and lungs.This takes about 30 minutes The breast wound and skin is surgically closed as usual.

Is Intrabeam TARGIT IORT Effective?

TARGIT IORT has been extensively tested in clinical trials over the past 20 years. The TARGIT-A trial, included 3451 patients treated in 33 hospitals in UK, Europe, USA and Australia and this trial compared TARGIT IORT with traditional radiotherapy. TARGIT IORT is given using the Intrabeam device. TARGIT IORT has only minimal side effects and they are fewer compared with traditional radiotherapy and the cosmetic outcome is similar to or better. The five-year results showed that when TARGIT is given at the same time as lumpectomy, the local-recurrence-free-survival is similar to traditional radiotherapy: 93.9% with TARGIT vs. 92.5% with traditional EBRT. As with all breast cancer treatments there is some uncertainty about the exact difference in local recurrence after TARGIT IORT compared with traditional radiotherapy. However, the UK National Institute of Care and Excellence have determined that such difference is very small (1 to 2%) and have recommended it for suitable patients in the NHS in hospitals that have the expertise and equipment.

Which patients could have taken part in the TARGIT-A trial

Women who were 45 or older with invasive ductal type cancer suitable for breast conservation (tumour size up to 3.5cm) were eligible to receive TARGIT IORT vs EBRT in the TARGIT-A trial. 3345 patients participated in TARGIT trial from 2000 to 2012, in 11 countries. ​ Click here for a web - tool to check suitability for Intrabeam TARGIT IORT

TARGIT-A Trial Design

In the randomised TARGIT-A trial, two policies of local radiation treatment are compared:

Design of the two parallel trials of immediate and delayed TARGIT-IORT

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

Some scientific publications related TARGIT-A trial

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 Futher details are at https://targit.org.uk ​ First publication of the main results (2010) ​ 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 (2014) ​ 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 Full final 226 page report of the TARGIT-A trial for the the National Institutes of Health Research, Department of Health, UK (2016) Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C, Brew-Graves C, Potyka I, Morris S, Vaidya HJ, Williams NR, Baum M. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technology Assessment 2016;20(73) TARGIT-A randomised clinical trial of TARGIT IORT using Intrabeam