Joint Hospital Surgical Grand Round

Joint Hospital Surgical Grand Round

Chiu Hiu Fung JenniferKwong Wah Hospital

25-1-2014

Chiu Hiu Fung JenniferKwong Wah Hospital

25-1-2014

Is Breast Conserving Treatment (BCT) feasible for Ipsilateral Breast Tumour Recurrence (IBTR)?

Breast conserving surgery

BCT = wide local excision + radiotherapy

Well-established treatment modality for early breast cancer

Equal local control and disease-free survival compared to mastectomy

Superior psychosocial outcomes - improved body image and lifestyle score

National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial

Definition of local recurrence

IBTR - recurrent tumour within the ipsilateral breast after lumpectomy + radiotherapy

Recurrence within 6 months of primary surgery - primary treatment failure

Local recurrence - recurrence after mastectomy ie skin / chest wall

True recurrence (TR) vs New primary (NP)

Ipsilateral breast tumour recurrence (IBTR) rate after BCS + RT is 1-2% per year

In 1990s, IBTR rate after BCS (without RT) at 10 years: 19%

In 2000s, IBTR rate after BCS + RT at 10 years: 9%

NSABP B-17 and B-24 trials

Risk factors for first recurrence:

Omission of radiotherapy

Young age

Involved margin

Multifocality

Extensive in-situ component

Lymphovascular invasion

No standard classification of True Recurrence (TR) vs New Primary (NP)

Different classifications include:

tumour location

histological subtype

ER status

DNA flow cytometry

Gene expression profiling data

True Recurrences: 44 - 78%

TR - shorter metastasis-free survival

mean time to disease recurrence -

37 months for TRs vs 55 months for NPs

Classification of ipsilateral breast tumor recurrence after breast-conserving therapy: New primary cancer allows a good prognosis. Nishimura S. Cancer 2005;12:112–117.

True recurrence is a poor prognostic factor - agressive biology intrinsic to the tumour itself

Lower overall survival and disease-free survival compared to NP group

Hypothesis that TR and NP tumours are distinct entities with different survival prognoses requires further confirmation with pathology review and molecular analyses

Analysis of Ipsilateral Breast Tumor Recurrences after Breast-conserving Treatment Based on the Classification of True Recurrences and New Primary Tumors. Komoike Y. Breast Cancer. 2005;12(2):104-111.

Treatment options for IBTR

Salvage mastectomy - gold standard of local treatment for IBTR

Second local recurrence rate: 10% (3-32%)

5 year disease free survival: 41-59%

5 year overall survival: 70% (58-84%)

Is there any role for repeating BCS for IBTR?

Is it safe?

<local treatment options for IBTR>

Four different salvage options were analyzed:

(a) Salvage mastectomy alone

(b) Salvage mastectomy + re-irradiation

(c) 2nd BCS alone

(d) 2nd BCS + re-irradiation

Methods of Re-irradiation

Conventional external beam re-irradiation

Interstitial brachytherapy

low dose rate, high dose rate, or pulsed dose rate

Intra-operative radiotherapy

Salvage mastectomy alone for IBTR

Second local recurrence rate 10-15% (3 - 32%)

10 year disease free survival: 40-45% (61 - 84%)

Second bcs without post-operative re-irradiation

Second local recurrence rate: 20% (7 - 32%)

10 year disease free survival: 60% (61 - 64%)Second BCS without re-irradiation is associated with more second local recurrence and less 10 year overall survival when compared to salvage mastectomy

Second local recurrence rate: 2 - 26%

5 year overall survival: 75% (61 - 97%)

Second bcs with post-operative re-irradiation for IBTR

Grade 3-4 toxicity: 3 - 11%

2nd local recurrence rate

5-year disease-free survival

(%)

5-year overall survival (%)

10-year overall survival (%)

Salvage mastectomy alone

10-15% 50% 60-65% -

Salvage mastectomy alone with post-op re-

irradiation2% 62% 59%

* distant metastasis rate

- 28%

Second breast-conserving surgery

alone

20% (7-32%)

78% - 50%

Second breast-conserving surgery with

re-irradiation

10%(0-26%)

60% 87% -

Salvage mastectomy vs second BCS + Re-irradiation

Second local recurrence rate is similar (about 10%)

5 year overall survival is similar, mainly influenced by distant metastatic progression

Difficult to conduct a randomized controlled trial

Large number of patients will be needed as IBTR is a rare event

Patient may not accept randomization between salvage mastectomy and second BCT

What are the risk factors for second local recurrence?

Retrospective analysis

3155 patients with DCIS or IDC underwent breast conserving surgery from 1986 - 2010

132 developed IBTR (~3%)

46 underwent salvage mastectomy, remaining 86 received second BCS

8 patients that did not receive re-irradiation were excluded

Total of 78 patient with IBTR and were treated with second BCS + re-irradiation

17 of 78 patients experienced second IBTR

Time >2 years

ER +ve

negative marginsage at diagnosis >40

yearsER +ve

Low risk: DFI > 2 years, ER positive or unknown, negative margins, and age at initial diagnosis >=40

Which type of patients are suitable for second BCS + re-irradiation?

Controversial...

Time to recurrence >2 years

Positive ER status

? new primary tumors

Sizeable breasts

Conclusion

Both salvage mastectomy and second BCS + re-irradiation are treatment options of IBTR

Still need further large scale studies to compare local recurrence rate and overall survival

To identify the group of patients who can benefit from second BCT

Develop newer radiation techniques to reduce re-irradiation toxicity

References

Local treatment options for ipsilateral breast tumour recurrence. Hannoun-Levi JM. Cancer Treat Rev. 2013 Nov;39(7):737-41.

Analysis of Ipsilateral Breast Tumor Recurrences after Breast-conserving Treatment Based on the Classification of True Recurrences and New Primary Tumors. Komoike Y. Breast Cancer. 2005;12(2):104-111.

Repeat Lumpectomy for Ipsilateral Breast Tumor Recurrence after Breast-Conserving Treatment. Ishitobi M. Oncology. 2011;81:381-386

True Recurrence Versus New Primary: An Analysis of Ipsilateral Breast Tumor Recurrences After Breast-Conserving Therapy. V Panet-Raymond. International Journal of Radiation Oncology. 2011;81(2):409-41

Repeating Conservative Surgery after Ipsilateral Breast Tumor Reappearance: Criteria for Selecting the Best Candidates. Gentilini O. Ann Surg Oncol. 2012;19:3771-3776

The End

interstitial brachytherapy

Brachy: short-distance

Can be used alone or in combination with surgery, external beam RT and chemotherapy

Intraoperative radiotherapy (IORT)

IORT group: 1 dose 21 Gy during surgery

External RT group: 50 Gy in 25 fractions of 2 Gy + boost of 10 Gy in 5 fractions

5-year rate for IBTR 4.4% for IORT group; 0.4% for external RT

Same overall survival

Significantly fewer skin side-effects in IORT group (p=0.0002)

Toxicity of irradiation

radiation dermatitis, fibrosis, telangiectasia

pericarditis, pericardial effusion, pneumonitis

From double surgery: asymmetry