radiotherapy for breast cancer

Locally Advanced Breast Cancer:Radiotherapy

Rob Dinniwell, MDRadiation Medicine ProgramPrincess Margaret Hospital, University of Toronto, Canada

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

3. Response Assessment and Adaptive Radiotherapy

4. Conclusion: Integration into treatment delivery5. Questions

Outline1. Individual Patient

52 year old womanpresents with: thickening in Rt breastmanaged initially with a naturopathprogressed to mass encompassing entire breast and associated lymphadenopathy

FUTURE• Improved imaging ⇒ validation

• Modulation of therapeutic intensity based on maps disease burden / biology

• Large robust clinical trials (RCT)

• Further improve techniques for streamlined integration of diagnostic MRI with diagnostic and therapeutic local interventions

Outline1. Individual Patient

cT4N1M0 Rt breast caER/PR –ve, Her2/NEU +veNeoadjuvant Chemotherapy AC -> Taxotere with HerceptinReaction during administration of 2nd cycle

3-dimensional Volume Rendering of a Pre-

Treatment CT Simulation Data

set:Anterior Projection

3-dimensional Volume Rendering of a Pre-

Treatment CT Simulation Data

set:Anterior Projection

3-dimensional Volume Rendering of a Pre-

Treatment CT Simulation Data

set:Axial Projection

3-dimensional Volume Rendering of a Pre-

Treatment CT Simulation Data

set:Axial Oblique Projection

3-dimensional Volume Rendering of a

Post-Treatment CT Simulation Data

set:Anterior Projection

3-dimensional Volume Rendering of a

Post-Treatment CT Simulation Data

set:Anterior Projection

Post-Treatment Axial

Pre-Treament: Axial

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

3. Response Assessment and Adaptive Radiotherapy

4. Integration into treatment delivery5. Conclusion

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationRegional Lymphatics

Visible Human Dataset

The Visible Human Male data set, axial images with pixel heights and widths of 0.14 mm and 1 mm axial slice spacing, and the Female data set, pixels measuring 0.33 mm x 0.33mm with 0.33 mm axial slice spacing, were obtained from National Institute of Health. The anatomical images of the Visible Human datasets consist of high-resolution axial sections and provide a useful reference.

High resolution thoracic axial section from the Visible Human Anatomic Series Relationship of adjacent lymph nodes (green arrow) to the adjacent vessels (red arrow).

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

Brachial plexus

Radiation-induced brachial plexopathy

Radiation-induced brachial plexopathy

Galecki, Acta Oncologica 2006

Brachial Plexus

• Phased array torso coil• Coronal STIR sequence• Oblique sagittal STIR with slice orientation

perpendicular to long axis of brachial plexus• Oblique sagittal T1• 20 subjects

Raphael, Anesthesiology 2005

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

Cone Beam CT

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

3. Response Assessment and Adaptive RadiotherapyMagnetic Resonance Imaging

GoalTo develop standardized imaging techniques that can non-invasively monitor response

To quantify changes in size and spread, as well as track specific biologic and physiologic markers of malignancy

To help predict response to therapy and facilitate patient specific treatment

Dynamic Contrast-Enhanced (DCE) MRI

delineate architectural and dynamic featuresof breast tumors and determine their size

develop standardized imaging techniques that can non-invasively monitor response

(DCE) MRI can provide information regarding pathophysiologic response of tumor vasculature

Dynamic Contrast-Enhanced (DCE) MRI

Tumor angiogenesis results in:• formation of blood microvessels excessively permeable and

enhanced leakage of bloodborne contrast agents• augmented contrast enhancement

Therapeutic response: • tumor angiogenesis halted• development of necrosis and fibrosis • establishment of a microcapillary network with properties

different from that feeding the growing tumor

Changes can be quantified by analyzing enhancement parameters of dynamic contrast-enhanced images

Dynamic Contrast-Enhanced (DCE) MRI

Tumor angiogenesis results in:• formation of blood microvessels excessively permeable and

enhanced leakage of bloodborne contrast agents• augmented contrast enhancement

Therapeutic response: • tumor angiogenesis halted• development of necrosis and fibrosis • establishment of a microcapillary network with properties

different from that feeding the growing tumor

Pre-

Post-

Changes can be quantified by analyzing enhancement parameters of dynamic contrast-enhanced images

Chou, Acad Radiol 2007

Dynamic Contrast-Enhanced (DCE) MRI

• Imaging at Weeks:0, 1, 4, 8, and pre-operatively

• GE 1.5-tesla MR scanner• 4 channel breast coil• Spoiled Gradient Recalled Sequence (SPGR)• Intravenous Gd-DTPA• Tumor size and modelling • 10 subjects

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

3. Response Assessment and Adaptive Radiotherapy

4. Conclusion: Integration into treatment delivery5. Questions

Postmastectomy radiotherapy

• A portion of patients remain at risk for local recurrence following surgery

• In those at risk, radiotherapy can:– Reduce local regional recurrence– Increase cause specific and overall survival

Oxford Overview• Mastectomy +/- Postmastectomy Radiotherapy

Local Recurrence

• 72% decrease

Lancet 366:2087, 2005

Survival

• 5% for those with +ve LN’s

Oxford Overview• Mastectomy +/- Postmastectomy Radiotherapy

Lancet 366:2087, 2005

Local-Regional Recurrence and Pathological Extent of

Disease• MD Anderson experience

• Mastectomy, chemotherapy and no radiation– 150 patients preoperative chemotherapy– 1031 patients postoperative chemotherapy

Buchholz et al., Int J Radiat Oncol Biol Phys, 2003

Pathological Size of Primary Tumor

0%5%

10%15%20%25%30%35%40%45%50%

0-2.0 cm 2.1-5.0 cm >5.0 cm

AdjuvantPreop

5-Year LRR

Pathological Nodal Status

0%

10%

20%

30%

40%

50%

60%

0 LN+ 1-3 LN+ 4 or > LN+

AdjuvantPreop

5-Year LRR

Local-Regional Recurrence Risk After Preoperative Chemotherapy

and Mastectomy• MD Anderson experience

• 150 patients, 1974 to 1998– Preoperative chemotherapy administered– Modified radical mastectomy performed– NO radiotherapy

Buchholz et al., JCO, 2002

Factors Associated with Local- Regional Recurrence

Pretreatment Factors• Clinical stage• Clinical T and N stage

Postoperative Factors• Number of + LNs• Primary tumor size

Buchholz et al., JCO, 2002

Postmastectomy Radiotherapy Following Neoadjuvant

Chemotherapy • MD Anderson experience• 676 patients treated with neoadjuvant

chemotherapy• Mastectomy• 134 patients NO radiotherapy• 542 patients radiotherapy

Huang et al., JCO, 2004

Comparison Between Groups

• Irradiated patients worse

Huang et al., JCO, 2004

0 200 400 600cT3-4

cN2-3

Min. R

espo

nse4 o

r > LN

s

Close/+

Mar

gins

No Radiotherapy

Radiotherapy

Percentage of Patients

Rate of Local-Regional Recurrence

Huang et al., JCO, 2004

XRT

No XRT

Local-Regional Recurrence Clinical Stage III to IV > pCR

Huang et al., JCO, 2004

XRT

No XRT

Local-Regional Recurrences in Patients with a pCR

Clinical Stage III Disease

McGuire et al., Int J Radiat Oncol Biol Phys, 2007 Jul 15;68(4):1004-9. Epub 2007 Apr 6.

67%

93%

n=12

n=62

Patients with Stage III Disease and a pCR

McGuire et al., Int J Radiat Oncol Biol Phys, 2007 Jul 15;68(4):1004-9.

41%

88%

Patients with Stage III Disease and a pCR

McGuire et al., Int J Radiat Oncol Biol Phys, 2007 Jul 15;68(4):1004-9.

33%

77%

Post mastectomy radiotherapy in Patients <35 Years with Stage II-III

Garg et al., Int J Radiat Oncol Biol Phys, 2007 Sep 12; [Epub ahead of print]

• MD Anderson experience

• 107 patients <35 years of age with IIA-IIIC– Treated with doxorubicin based preoperative

chemotherapy – Modified radical mastectomy performed– +/- radiotherapy

Post mastectomy radiotherapy in Patients <35 Years with Stage II-III

Garg et al., Int J Radiat Oncol Biol Phys, 2007 Sep 12; [Epub ahead of print]

• 80 PMRT vs 27 no PMRT• PMRT group showed:

– Better LRC (88% vs 63% at 5 years)– Better OS (67% vs 48% at 5 years)

• “benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions”

Determining and Individualizing Radiotherapy Treatment Fields

A majority of women receiving neoadjuvant chemotherapy have a

downstaging of their pathology.

The use of the remaining pathological extent of disease alone to determine the likelihood of local

regional recurrence is not appropriate.

Controversies • A conservative (but aggressive) approach would be to

recommend radiation to all LABC patients • However, patients with little or no residual breast/axillary

disease following neoadjuvant chemotherapy may not derive a significant benefit regional radiotherapy.

• Existing data are limited.

Radiation• At least four metastatic lymph nodes or 5 cm of residual

disease in the breast after chemotherapy clearly benefit from locoregional irradiation

• All lumpectomy patients require breast irradiation

• Post-Mastectomy• Pretreatment stage III or cT3 tumors• > or = 4 LN’s +• ? Pretreatment stage II disease with high risk features

Outline1. Individual Patient2. Anatomy:

Target Volume DelineationOrgans at Risk

3. Response Assessment and Adaptive Radiotherapy

4. Conclusion: Integration into treatment delivery5. Questions