Radiation Therapy in Breast Cancer

MOTP Seminar January 2009

Jacqueline Spayne MD PhD FRCPC

Department of Radiation Oncology

Odette Cancer Centre

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

Breast conserving therapy

Post-mastectomy

Radiation target volumes

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Adjuvant radiation following

breast conserving surgery (BCS)

in early breast cancer (EBC)

• 6 (important) RCTs of mastectomy vs lumpectomy + XRT

– Equivalent OS and acceptable LC

From CCO Guidelines, see:http://www.cancercare.on.ca/pdf/full1_2.pdf

Adjuvant radiation following BCS in EBC

• 4 RCTs of Lumpectomy +/- XRT

From CCO Guidelines, see:

http://www.cancercare.on.ca/pdf/full1_2.pdf

Adjuvant radiation following BCS in EBC

Adjuvant radiation following BCS in EBC

Meta-analyses• EBCTCG Lancet 2000/Cochrane2002

- 40 trials – 1950s-1980s (inc some mastectomy)

- 10yr LRR reduced from 27% to 9%

- 5% absolute breast cancer mortality benefit

- No OS benefit with increased non-BC deaths

• Vinh-Hung JNCI 2004

- 15 trials (BCS only)

- IBT recurrence RR 3.00 with no RT

- 8.6% mortality benefit with RT

Post-mastectomy RadiationRCTs of mastectomy +/- XRT

Danish premenopausal (Overgaard NEJM 97)

10y LRR 10y OS

CMF 32% 45%

CMF+RT 9% 54%

Danish post-menopausal (Overgaard Lancet 99)

10y LRR 10y OS

Tam 35% 36%

Tam+RT 8% 45%

Post-mastectomy RadiationBC Trial – 20yr update (Ragaz JNCI 2005)

318 Premenopausal N+, CMF chemo

LRR-free Survival

Postmastectomy RadiationBC Trial – 20yr update (Ragaz JNCI 2005)

318 Premenopausal N+, CMF chemo

Overall Survival

Post-mastectomy Radiation Meta-analysis

EBCTCG Lancet 2005

Post-mastectomy Radiation Meta-analysis Gebski et al JNCI 2006

Post-mastectomy Radiation Meta-analysis Gebski et al JNCI 2006

Post-mastectomy Radiation Indications

• Node positive

• T3, T4

• Other risk factors

– Grade 3

– +LVI

– Positive margins

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

Breast conserving therapy

Post-mastectomy

Radiation target volumes

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Adjuvant radiation in Breast Cancer

– Target Volumes• RT-geekspeak – GTV, CTV, PTV• Post BCS

– Breast, underlying chest wall

• Post-mastectomy– Chest wall

• N2 disease– Supra-clavicular fossa– ?Axilla, IMN

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

Breast conserving therapy

Post-mastectomy

Radiation target volumes

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Radiation in Breast Cancer - Toxicity• Breast tangents alone – RT well tolerated

• Acute - common

– Skin

– Fatigue

• Sub-acute – very rare

– Pneumonitis

• Late – very rare

– Lung

– Cardiac

– 2nd malignancies

• Except - Pigmentation, fibrosis, telangiectasia – up to 30% depends on technique

Radiation in Breast Cancer - Toxicity

• Additional late toxicity of nodal irradiation

• Lymphedema

• BC trial – 9% vs 3%; Danish trials – 14% vs 3%

• Pneumonitis

• BC trial – 1 patient (0.6%)

• Impaired shoulder ROM

• Danish trials – 16% vs 2%

Radiation in Breast Cancer - Toxicity• Additional late toxicity of nodal irradiation cont’d

• Asymptomatic lung fibrosis

• Danish trial – 60% vs ?0%

• Chronic pulmonary symptoms – ??

• Neurological

• Danish trial - paresthesia/hyperesthesia 21% vs 7%

• slight decreased strength – 14% vs 2%

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation for 1-3 LN+

• Radiation of IMC nodes

• 3 vs 4 field for supraclavicular fossa

• Patient selection after neo-adjuvant chemo

Can adjuvant RT be omitted in some patients?

• Canadian trial (Fyles NEJM 2004)

769 pts, >50y, T1/2N0, clear margins, on Tam

5y LR 5yDFS 5y OS

All pts – no RT 7.7% 84% 93%

All pts - + RT 0.6%* 91%* 93% (NS)

T1 ER+ - no RT 5.9%

T1 ER+ - + RT 0.4%*

>60y, T</=1cm, ER+ - no RT 1.2% (Unplanned analysis)

>60y, T</=1cm, ER+ - +RT 0% NS

Can adjuvant RT be omitted in some patients?

• CALGB C9343 (Hughes NEJM 2004)

636 pts, >70y, T1N0, clear margins, ER+, on Tamoxifen

5y LRR 5y OS

No RT 4% 86%

+RT 1%* 87%

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation for 1-3 LN+

• Radiation of IMC nodes

• 3 vs 4 field for supraclavicular fossa

• Patient selection after neo-adjuvant chemo

Radiation Protocols

• Standard adjuvant treatment – 50Gy in 25 fractions

• Canadian hypofractionation trial (Whelan JNCI 2002)

4250/16 equivalent to 5000/25 to breast only in selected pts

• EORTC boost trial (Bartelink NEJM 2001)

50/25 50/25+16/8boost

LR all pts 7.3% 4.3%*

</=40y 19.5% 10.2%*

41-50 9.5% 5.8%*

>50 4.1% 3%NS

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation for 1-3 LN+

• Radiation of IMC nodes

• 3 vs 4 field for supraclavicular fossa

• Patient selection after neo-adjuvant chemo

Partial Breast Radiation

• Techniques

– Intra-operative (Mammosite)– Catheter HDR– Seeds– External beam

• Short-term follow-up only• Remains experimental

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation for 1-3 LN+

• Nodal radiation fields

• Patient selection after neo-adjuvant chemo

Nodal irradiation with 1-3 +ve nodes• Post-lumpectomy – no

– Consider if:

– <4-6 (?) nodes dissected

– Other bad prognostic features (eg large T, LVI, young, ECE)

– MA20 trial - closed

• Post-mastectomy

– Guidelines equivocal

– Meta-analysis supports chest-wall radiation for N1

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation for 1-3 LN+

• Nodal radiation fields

• Patient selection after neo-adjuvant chemo

Nodal radiation fields• Radiation of IMC chains

– Most trials included IMC

– Practice variable

– Usually only include with IQ tumours and/or N+++

– Techniques variable – risk of increased toxicity

• Addition of posterior SC (deep axillary) field

– Inadequate axillary clearance

– ??ECE

– Toxicity risk

Adjuvant RT in Breast Cancer - Controversies

• Omission of radiation in selected patients

• RT protocols - Fractionation & boost

• Partial breast radiation

• Nodal radiation

– Indications: N1 vs N2; post BCS vs post-mastectomy

– Target nodes: axilla, SCF, IMC

• Patient selection after neo-adjuvant chemo

Adjuvant Radiation after Neoadjuvant Chemo

• No randomized data

• MDACC 6 neoadjuvant chemo trials

542 patients chemo, mast’y, + RTvs

134 patients chemo, mast’y, no RT

Huang et al JCO 2004

Adjuvant Radiation after Neoadjuvant Chemo

Huang et al JCO 2004

Adjuvant Radiation after Neoadjuvant ChemoCause-Specific Survival – Stage 3B

Huang et al JCO 2004

Adjuvant Radiation after Neoadjuvant Chemo…….even after pCR

McGuire et al in press

Adjuvant Radiation after Neoadjuvant Chemo…….even after pCR

McGuire et al in press

Adjuvant Radiation after Neoadjuvant Chemo

• Policy

– All LABC patients offered adjuvant

radiation

– Chest wall + regional lymph nodes

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

Breast conserving therapy

Post-mastectomy

Radiation target volumes

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Salvage Radiation for Breast Cancer

• Can have dramatic responses

• Huang et al IJROBP 200238 inoperable patients after anthracycline

regimen

Salvage Radiation for Breast Cancer

38 patients inoperable after chemo

Loco-regional radiation

32 had mastectomy

6 year follow-up5 LRR alone

21 distant mets3 both

9 disease free

Huang et al IJROBP 2002

Neoadjuvant Radiation for Breast Cancer

• TRIAL– Neoadjuvant concurrent chemoradiation in LABC

Radiation Treatment in Breast Cancer

• Adjuvant Radiotherapy

Breast conserving therapy

Post-mastectomy

Radiation target volumes

• Toxicities

• Controversies

• Salvage Radiation

• RT for recurrence & metastases

Radiation for Recurrence & Metastases• Recurrence

– In-breast → mastectomy

– Chestwall → consider radiation

depends on previous treatment, time interval, prognosis, other treatment options etc

• Metastases

– Whole other topic!!!!

QUESTIONS……..