1. Locally Advanced Breast Cancer:
Radiotherapy
Rob Dinniwell, MD
Radiation Medicine Program
Princess Margaret Hospital, University of Toronto, Canada

2. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
3. Response Assessment and Adaptive
Radiotherapy
4. Conclusion: Integration into treatment delivery
5. Questions

3. Outline
1. Individual Patient
52 year old woman
presents with: thickening in Rt breast
managed initially with a naturopath
progressed to mass encompassing
entire breast and associated
lymphadenopathy

4. •
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

5. Outline
1. Individual Patient
cT4N1M0 Rt breast ca
ER/PR –ve, Her2/NEU +ve
Neoadjuvant Chemotherapy AC ->
Taxotere with Herceptin
Reaction during administration of 2nd cycle

6. 3-dimensional Volume
Rendering of a Pre-
Treatment CT
Simulation Data
set:
Anterior Projection

7. 3-dimensional Volume
Rendering of a Pre-
Treatment CT
Simulation Data
set:
Anterior Projection

8. 3-dimensional Volume
Rendering of a Pre-
Treatment CT
Simulation Data
set:
Axial Projection

9. 3-dimensional Volume
Rendering of a Pre-
Treatment CT
Simulation Data
set:
Axial Oblique Projection

10. 3-dimensional Volume
Rendering of a
Post-Treatment CT
Simulation Data
set:
Anterior Projection

11. 3-dimensional Volume
Rendering of a
Post-Treatment CT
Simulation Data
set:
Anterior Projection

12. Pre-Treament:
Axial
Post-Treatment
Axial

27. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
3. Response Assessment and Adaptive
Radiotherapy
4. Integration into treatment delivery
5. Conclusion

28. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Regional Lymphatics

31. 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.

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

38. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
Brachial plexus

40. Radiation-induced brachial plexopathy

41. Radiation-induced brachial plexopathy
Galecki, Acta Oncologica 2006

42. 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

43. Raphael, Anesthesiology 2005

45. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
Cone Beam CT

46. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
3. Response Assessment and Adaptive
Radiotherapy
Magnetic Resonance Imaging

47. Goal
To 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

48. Dynamic Contrast-Enhanced
(DCE) MRI
delineate architectural and dynamic features
of 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

49. 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

50. 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

51. Pre-
Post-
Changes can be quantified by analyzing enhancement parameters of
dynamic contrast-enhanced images
Chou, Acad Radiol 2007

52. 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

53. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
3. Response Assessment and Adaptive
Radiotherapy
4. Conclusion: Integration into treatment delivery
5. Questions

54. 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

55. Oxford Overview
• Mastectomy +/- Postmastectomy Radiotherapy
Local Recurrence
• 72% decrease
Lancet 366:2087, 2005

56. Oxford Overview
• Mastectomy +/- Postmastectomy Radiotherapy
Survival
• 5% for those
with +ve LN’s
Lancet 366:2087, 2005

57. 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

58. Pathological Size of Primary
Tumor
50%
45%
40%
35%
5-Year
LRR 30%
25% Adjuvant
20% Preop
15%
10%
5%
0%
0-2.0 cm 2.1-5.0 cm >5.0 cm

59. Pathological Nodal Status
60%
50%
5-Year 40%
LRR
30% Adjuvant
Preop
20%
10%
0%
0 LN+ 1-3 LN+ 4 or > LN+

60. 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

61. 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

62. 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

63. Comparison Between Groups
• Irradiated patients
worse
ns
gi
ar
M
/+
s
No Radiotherapy
LN
se
lo
>
Radiotherapy
C
or
e
4
ns
po
es
.R
3
2-
in
cN
M
4
3-
cT
0 200 400 600 Percentage of Patients
Huang et al., JCO, 2004

64. Rate of Local-Regional Recurrence
No XRT
XRT
Huang et al., JCO, 2004

65. Local-Regional Recurrence
Clinical Stage III to IV > pCR
No XRT
XRT
Huang et al., JCO, 2004

66. Local-Regional Recurrences in
Patients with a pCR
93% n=62
67% n=12
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. Patients with Stage III Disease
and a pCR
88%
41%
McGuire et al., Int J Radiat Oncol Biol Phys, 2007 Jul
15;68(4):1004-9.

68. Patients with Stage III Disease
and a pCR
77%
33%
McGuire et al., Int J Radiat Oncol Biol Phys, 2007 Jul
15;68(4):1004-9.

69. Post mastectomy radiotherapy in
Patients <35 Years with Stage II-III
• MD Anderson experience
• 107 patients <35 years of age with IIA-IIIC
– Treated with doxorubicin based preoperative
chemotherapy
– Modified radical mastectomy performed
– +/- radiotherapy
Garg et al., Int J Radiat Oncol Biol Phys, 2007 Sep 12;
[Epub ahead of print]

70. Post mastectomy radiotherapy in
Patients <35 Years with Stage II-III
• 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”
Garg et al., Int J Radiat Oncol Biol Phys, 2007 Sep 12;
[Epub ahead of print]

71. Determining and Individualizing
Radiotherapy Treatment Fields

72. 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.

73. 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.

74. 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

75. Outline
1. Individual Patient
2. Anatomy:
Target Volume Delineation
Organs at Risk
3. Response Assessment and Adaptive
Radiotherapy
4. Conclusion: Integration into treatment delivery
5. Questions