Background

•  The Z-11 trial found that omission of axillary clearance even after finding one or two positive sentinel nodes, does not affect local control, despite 23% of patients having residual disease1. However, every patient in this trial received whole breast external beam radiotherapy (EBRT)

•  Prevalent deduction Inadvertent non-therapeutic irradiation of the lower axilla with tangential fields of whole breast radiotherapy might be essential to treat the minimal residual axillary disease. Therefore, patients receiving partial breast radiation (PBI) or IORT or TARGIT may not be suitable for the sentinel node biopsy and may need axillary clearance if 1 or 2 positive sentinel nodes are found.

•  The TARGIT- A trial compared conventional fractionated external beam radiotherapy (EBRT), with the risk adapted approach using single dose targeted intraoperative radiotherapy (TARGIT)2; if if high risk factors are found subsequently, protocol recommended EBRT in addition to TARGIT(in 15-20% of cases).

Results

•  91% of patients had sentinel node biopsy, of which 90% had <10 nodes removed if that was negative.

•  Generally good prognosis patients, but

•  1347 patients were less than 61 years old

•  502 patients had nodes involved with cancer

•  Total 9491 women-years of follow up

Method

•  Non-randomised comparison as per treatment received in the TARGIT-A trial

•  Group A received no EBRT

•  Group B received EBRT

References

1.  Giuliano AE, Hunt KK, Ballman KV,Beitsch PD, Whitworth PW..., Morrow M. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. J A M A : the journal of the American Medical Association 2011;305(6):569-75

2.  Vaidya JS, Joseph DJ, Tobias JS, …, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 2010 Jul 10;376(9735):91-102.

3.  Vaidya JS, Wenz F, Bulsara M, Joseph D, Tobias J..., Baum M. Targeted intraoperative radiotherapy for early breast cancer: TARGIT-A trial updated analysis of local recurrence and first analysis of survival. San Antonio Breast Cancer Symposium, General Session 4, Dec 6, 2012. Cancer Res; 2012;72Suppl24:100s-101s http://goo.gl/E410I

Jayant S Vaidya1 ,Max Bulsara2, Frederik Wenz3, Samuele Massarut4, David Joseph5, Jeffrey S Tobias1, Norman Williams1, Michael Baum1;

1London UK, 2Fremantle AU, 3Mannheim DE, 4Aviano IT, 5Perth AU, on behalf of the TARGIT Trialists’ Group

Omitting whole breast radiotherapy does not increase axillary recurrence: Data from TARGIT-A trial

TARGIT-A trial randomisation

Excision of cancer

+ Concurrent TARGIT

Breast cancer patient

(>=45 years) suitable for

breast conserving

surgery

For this paper, these two groups of patients were

analysed in a non-randomised

comparison

Excision of cancer

+ EBRT

Randomisation: Risk-adapted

vs. Conventional

A

B

No EBRT given

(TARGIT alone)

EBRT given

A B

•  Radiation delivered to the tumour bed, immediately after lumpectomy under the same anaesthetic

•  Focussed to the tissues at highest risk of recurrence

•  Mobile machine used in a standard operating room

•  Physical dose of 20Gy to the tumour bed, over ~25 min

•  No radiation to the axilla unless EBRT is added

No EBRT given (TARGIT alone)

Total

1613 patients

Axillary recurrence 5 patients

5- year risk

0.68% (95%CI 0.28-1.6)

EBRT given

Total 1762 patients

Axillary recurrence

6 patients

5- year risk 0.82%

(95%CI 0.34-2.02)

0%

5%

10%

Axilla

ry re

curre

nce

1762 1448 1132 811 574 362TARGIT alone No EBRT1613 1047 791 548 403 231EBRT given

Number at risk

0 1 2 3 4 5Years

EBRT givenTARGIT alone: No EBRT

EBRT vs No EBRTAxillary recurrence

HR 0.84 (0.26- 2.74) p=0.8

Number of patients Median Follow up

1222 5 years 2020 4 years 3451 2 years 5 months

3375 patients had breast conserving surgery

Does omission of EBRT increase axillary recurrence in the TARGIT-A trial?

Jayant S Vaidya, David J Joseph, Jeffrey S Tobias, Max Bulsara, Frederik Wenz, Christobel Saunders, Michael Alvarado, Henrik L Flyger, Samuele Massarut, Wolfgang Eiermann, Mohammed Keshtgar, John Dewar, Uta Kraus-Tiefenbacher, Marc Sütterlin, Laura Esserman, Helle M R Holtveg, Mario Roncadin, Steffi Pigorsch, Marinos Metaxas, Mary Falzon, April Matthews, Tammy Corica, Norman R Williams, Michael Baum Conclusion 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.

Primary End Point : Absolute difference in Ipsilateral Breast Recurrence (IBR) In unselected cases When TARGIT is given concurrent with lumpectomy, TARGIT minus EBRT= 1.0% (SE 0.9) When TARGIT is given as a delayed second procedure, TARGIT minus EBRT= 3.7% (SE 1.9)

Secondary End Point : Overall Survival

Compared with EBRT, TARGIT results in: - Significantly fewer non-breast-cancer deaths

(Difference -2.1% p=0.0086) - Leading to a trend for reduced overall mortality

(Difference -1.4% p=0.099)

June 2010 ASCO First results of the TARGIT-A trial1

December 2010 San Antonio Breast Cancer Symposium3

Updated results of the TARGIT-A trial and first analysis of survival 3451 patients from 33 centres in 10 countries (trial closed in June 2012)

As TARGIT does not treat the axilla, any difference in outcome of the axilla may be attributed to EBRT.

Non-randomised comparison

TARGIT: TARGeted Intraoperative radioTherapy

If high risk factors: EBRT

No further radiotherapy

•  Of the 11 axillary recurrences, 10 had negative sentinel node biopsy (1 had axillary clearance)

•  EBRT did not make a difference to this risk of axillary recurrence.

•  Therefore, a falsely negative sentinel node biopsy is not compensated by the inadvertent irradiation of the axilla by standard EBRT.

•  The results were similar if we only included patients with 1or 2 positive nodes: EBRT given (1/255) vs. EBRT not given (0/127).

Conclusion

•  Omitting whole breast radiotherapy after a sentinel node biopsy in this good-prognosis population does not increase axillary recurrence rate.

•  Partial breast irradiation can be safely used in conjunction with routine sentinel node biopsy

Compare the risk of axillary recurrence