radiotherapy for breast cancer
DESCRIPTION
TRANSCRIPT
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