RADIOTHERAPY FOR BREAST CANCER
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  • 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
  • 13. 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
  • 14. Outline 1. Individual Patient 2. Anatomy: Target Volume Delineation Regional Lymphatics
  • 15. 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.
  • 16. High resolution thoracic axial section from the Visible Human Anatomic Series Relationship of adjacent lymph nodes (green arrow) to the adjacent vessels (red arrow).
  • 17. Outline 1. Individual Patient 2. Anatomy: Target Volume Delineation Organs at Risk Brachial plexus
  • 18. Radiation-induced brachial plexopathy
  • 19. Radiation-induced brachial plexopathy Galecki, Acta Oncologica 2006
  • 20. 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
  • 21. Raphael, Anesthesiology 2005
  • 22. Outline 1. Individual Patient 2. Anatomy: Target Volume Delineation Organs at Risk Cone Beam CT
  • 23. Outline 1. Individual Patient 2. Anatomy: Target Volume Delineation Organs at Risk 3. Response Assessment and Adaptive Radiotherapy Magnetic Resonance Imaging
  • 24. 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
  • 25. 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
  • 26. 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
  • 27. 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
  • 28. Pre- Post- Changes can be quantified by analyzing enhancement parameters of dynamic contrast-enhanced images Chou, Acad Radiol 2007
  • 29. 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
  • 30. 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
  • 31. 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
  • 32. Oxford Overview • Mastectomy +/- Postmastectomy Radiotherapy Local Recurrence • 72% decrease Lancet 366:2087, 2005
  • 33. Oxford Overview • Mastectomy +/- Postmastectomy Radiotherapy Survival • 5% for those with +ve LN’s Lancet 366:2087, 2005
  • 34. 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
  • 35. 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
  • 36. Pathological Nodal Status 60% 50% 5-Year 40% LRR 30% Adjuvant Preop 20% 10% 0% 0 LN+ 1-3 LN+ 4 or > LN+
  • 37. 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
  • 38. 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
  • 39. 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
  • 40. 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
  • 41. Rate of Local-Regional Recurrence No XRT XRT Huang et al., JCO, 2004
  • 42. Local-Regional Recurrence Clinical Stage III to IV > pCR No XRT XRT Huang et al., JCO, 2004
  • 43. 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.
  • 44. 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.
  • 45. 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.
  • 46. 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]
  • 47. 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]
  • 48. Determining and Individualizing Radiotherapy Treatment Fields
  • 49. 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.
  • 50. 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.
  • 51. 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
  • 52. 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