TARGIT A

TARGIT A  summary for Health Professionals

The traditional treatment for breast cancer has been removal of the whole breast (mastectomy). However, removal of only the lump (lumpectomy) and the lymph nodes, followed by radiotherapy to the preserved breast, has been shown to be just as effective at preventing the return of the tumour. However, radiotherapy takes up to six weeks of daily hospital visits. Many women find this inconvenient, costly and exhausting, and some women choose a mastectomy instead.

Beginning in 1996 a team at UCL developed a device that can deliver all the radiotherapy just after lumpectomy, while the patient is still in the operating theatre, called targeted intraoperative radiotherapy (TARGIT). The science behind TARGIT is well established: the tissues closest to the tumour are treated, rather than the whole breast. The TARGIT technique itself is now well established (FDA approval and CE mark) and the technology is available at over 50 centres worldwide (5 in the UK).

The CTG began a clinical trial to test this idea in March 2000 at UCL in London. The trial has subsequently attracted worldwide support: 21 centres in 7 countries (UK, USA, Germany, Italy, Poland, Canada and Australia) are actively participating, each with local funding, and all are administered from the UCL trial centre.

It is important to recognise that the trial is pragmatic and is testing two policies - rather than two techniques. In other words, it is not to test intraoperative (IORT) vs externally delivered radiotherapy (EBRT) but to test a pragmatic policy of IORT (in 100%) +/-EBRT (in ~15%) vs. EBRT (in 100%) i.e., The novel approach is to use IORT in potentially eligible patients, and add EBRT only if an unexpectedly higher risk is found post-operatively - which becomes necessary in 15% of cases. It is already known that the combination of IORT+ EBRT is safe and very effective.

The media have shown considerable interest in the TARGIT Trial, for example: BBC's Tomorrow's world (Nov 2000), ITV's London Today (Nov 2000), Time magazine (10 June 2002), Readers' digest (Oct 2003, Oct 2006), BBC News several times (latest at http://news.bbc.co.uk/1/hi/health/10239478.stm) and during the Cancer Week in 2007, and an article in New Statesman (7 Jan 2008). The message (radiotherapy given once -and only once- at surgery) seems to be readily understood. Politicians have also been interested (two appearances in the House of Commons in 2007), perhaps driven by the considerable convenience and benefit to the patient and the potentially significant cost saving to the NHS.

A manuscript describing early results was fast tracked and published in The Lancet (online first on 5 June and in the print on 9 July 2010, see reference). Local recurrence rates in the two groups were very low and similar at 4 years, by which time the greatest risk of local recurrence had passed (EBRT group 0.95% and TARGIT group 1.2%)*. The TARGIT approach had fewer radiotherapy related side effects. The conclusion in The Lancet stated “For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks”

Reference: 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.

*The statistics: The actual difference between the TARGIT and EBRT groups was 0.25% (10 times less than our original acceptable limit of 2.5%) at 4 years. As is usual while reporting clinical trials, not all patients have reached the follow up period of 4 years, so a standard statistical method was used to estimate a range around the 0.25% difference. This range, called 95% confidence interval, was -1% to +1.5%, which means that, with a 95% probability, at worst TARGIT is 1.5% worse than EBRT and at best TARGIT is 1% better than EBRT.

The TARGIT trial continues with a protocol-specified accrual goal of 3432 patients. The recruitment rate is currently about 480 patients/year and the target is expected to be reached in mid 2012.

If proven equivalent to whole breast radiotherapy, the TARGIT treatment could save time (for the patient and the health care providers), money (because the treatment is much less than half the cost of conventional treatment) and breasts (because many more women worldwide would avail of breast conserving therapy).

TARGIT A  Summary for Participants

“About 70% of patients with breast cancer are eligible for breast-conserving surgery (a lumpectomy), after which the remaining breast is treated with radiotherapy; this avoids a full mastectomy.

Traditionally, external beam radiotherapy (EBRT) is delivered to the entire breast in small doses every day for 3–6 weeks, necessitating patients to travel to and from the radiotherapy centre every working day. This can be impractical and strenuous.

The TARGIT (TARGeted Intraoperative radioTherapy) procedure precisely delivers radiation in a single dose during the lumpectomy operation over 15–35 minutes, using a ball-shaped device that is placed in the space where the tumour was. This way, unnecessary potentially harmful radiation to healthy tissues (skin, heart, lungs, etc.) is avoided and the areas nearest to the tumour site receive the most radiation. In this way, four-fifths of patients avoid EBRT altogether.

The TARGIT-A (TARGeted Intraoperative radioTherapy Alone) trial compared TARGIT with EBRT in 3451 patients who were aged ≥ 45 years and found that, when TARGIT is given with lumpectomy, the control of breast cancer is much the same as with EBRT. The chances of being alive without return of cancer in the breast at 5 years were 93.9% with TARGIT during lumpectomy and 92.5% with EBRT. Compared with EBRT, TARGIT had fewer side effects and fewer deaths from heart attacks or other cancers. TARGIT would be less expensive than EBRT, potentially saving the NHS up to £9.1 million a year, without considering the cost savings to patients.

Targeted intraoperative radiotherapy during lumpectomy is an effective, safer and less expensive option for eligible patients. ”

http://www.journalslibrary.nihr.ac.uk/hta/volume-20/issue-73#plain-english-summary

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Key publications

  • Year 2016 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)

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.

Health Technol Assess 2016;20(73)

DOI: http://dx.doi.org/10.3310/hta20730

Prof Jayant S Vaidya PhD, Prof Frederik Wenz MD, Prof Max Bulsara PhD, Prof Jeffrey S Tobias FRCR, Prof David J Joseph FRACR, Prof Mohammed Keshtgar PhD, Henrik L Flyger MD, Samuele Massarut MD, Michael Alvarado MD, Prof Christobel Saunders FRACS, Prof Wolfgang Eiermann MD, Marinos Metaxas PhD, Elena Sperk MD, Prof Marc Sütterlin MD, Douglas Brown FRCS, Prof Laura Esserman MD, Mario Roncadin MD, Prof Alastair Thompson FRCS, Prof John A Dewar FRCR, Helle M R Holtveg MD, Steffi Pigorsch MD, Mary Falzon FRCPath, Eleanor Harris MD, April Matthews BSc, Chris Brew-Graves MSc, Ingrid Potyka PhD, Tammy Corica BSc, Norman R Williams PhD, Prof Michael Baum MD, on behalf of the TARGIT trialists' group

The Lancet, Early Online Publication, 11 November 2013

doi:10.1016/S0140-6736(13)61950-9

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, Sütterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M.

Lancet. 2010 Jul 10;376(9735):91-102.