TARGeted Intra-operative radioTherapy (TARGIT) for breast cancer - a randomised trial Jayant Vaidya,...

TARGeted Intra-operative radioTherapy (TARGIT)

for breast cancer - a randomised trial

Jayant Vaidya, Michael Baum, Jeff Tobias, Joan Houghton,Mo Keshtgar,

Irving Taylor, Richard Sainsbury,

Derek D’Souza, S Morgan, M Metaxas, K Harte, A Sliski, E Thomson

Local treatment of breast cancer

Have the principles really changed?

Halsted’s Radical Mastectomy

Limited Surgery plus Radical Radiotherapy

Radiotherapy typically takes 6wks to deliver

Patients don’t like these 30 daily visits

Geography prevents many women from

receiving conservative breast surgery

Breast cancer = 1/3rd of RT work-load

Long waiting lists in many centres

Are there any problems with current approach?

The Solution

A novel radiotherapy technique that will accurately deliver all the necessary radiotherapy in ONE sitting

Treat only the index quadrant of breast

The RationaleWhole organ analysis of mastectomy specimens*

3-D analysis 63% harbour

occult cancer 80% of these

are in other quadrants

*Vaidya et al, Br. J. Cancer; 1996

The Rationale

but, in trials of conservative surgery:>90% recurrences occur in the index

quadrant

- whether radiotherapy is given or not

The occult cancers in other quadrants of the breast are probably not the cause of local recurrence.

Radiation to the index quadrant alone might be sufficient

Targeted Intra-operative Radiotherapy: (Targit)

A Novel Approach

The Technique

PRS400 (Intrabeam)A miniature electron generator and

accelerator

Accurately delivers radiotherapy from within the breastin about 25 minutes.

0 5 10 15 20

1

5

9

13

17

21

25

20 Gy at 2mm

1 Gy at 27mm

•Soft X-rays

•Small ‘very-high-dose’ region

•Quick attenuation (1/r3)-

– distance protects normal tissues

•Shielding is easy

Physical radiation dose

Applicator is inserted and purse string is tiedApplicator is inserted and purse string is tied

Rather than the complicated conformation of the source

to the target...

the target - the pliable breast tissue -

is conformed to the source

Targit with PRS

Estimated Biologically equivalent radiation dose (BED)

2mm e.g. breast 12 Gy 53 Gy

10mm e.g. skin

12 Gy 7 Gy

Distance from applicator

External

Boost /=10 /=1.5

121 Gy

21 Gy

1. To test the the TARGIT technique -its feasibility and safety

2. To test the approach of treating only the index

quadrant

Early operable breast cancer: <4cm in size

Phase I/II studyJuly 1998-Jan 2000

Wide Local excision + axillary surgery

Boost radiation with Photon Radio Surgery (PRS) intra-operatively

Whole breast radiotherapy post-op

Results – the pilot study

25 patients treated

With tumours ranging from 0.42 -4 cm

No major complicationsNo recurrences

Median follow up 30 m

Cosmetic results are good

ComplicationsOur 3rd patient had radionecrosis of skin

near the scar- skin was too close to the applicator

9 months

28 months

Cosmetic ResultsCosmetic Results

1) Photographs2) Patient’s own assessment of the

cosmetic result – appearance and texture:a) What would be your expected score

(out of 10)?b) What is the actual score (out of 10)

Satisfaction index = Actual / Expected

Cosmetic ResultsCosmetic Results

Satisfaction index (observed/expected)

Mean 95% CI

Appearance 1.2 (1.1-1.4)Texture 1.2 (1.0-1.4)

In only 4 out of the 25 patients in the pilot study, was the observed less than

expected.

Breast cancer - breast conserving therapy

RandomisationStudy Arm Control Arm

Wide local excision of primary tumour +

SNB/ axillary dissection + Targeted

Intraoperative Radiotherapy

(If histopathology is Lobular or EIC, add

5wks of postoperative radiotherapy)

Wide local excision of primary tumour

+SNB/ axillary dissection +6 wks of

Postoperative Radiotherapy

1st patient randomised on 29 March 2000

- 29 patients randomised until June 2001No complications in the IORT arm

1 wound infection in the post-op RT arm

Cosmetic appearance is good

No recurrences to date

Median follow up is 15 months

If proven, Targit could

Save up to 1/3rd of the workload of radiotherapy units world-wide

Allow women from remote areas to avail of breast conserving therapy