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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. - PowerPoint PPT Presentation
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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……..