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Ablative Therapy for Breast Cancer

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Presented as a Breakfast Symposium at the American Society of Breast Surgeons Annual Meeting May 2012, Phoenix, AZ

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Ablative Therapy for Breast Cancer

  1. 1. Ablative Therapy for Breast Cancer American Society of Breast Surgeons Annual Meeting Phoenix 2012
  2. 2. Disclosure Consultant: IceCure Medical
  3. 3. Ablative Therapy for Breast Cancer Treatment • No compromise to local control or overall survival with a less aggressive surgical approach • Lumpectomy problems: anesthesia, scarring, potential for cosmetic deformity, potential for multiple operations • More breast surgeons becoming involved with image-guided procedures • Ablative therapy just makes sense!
  4. 4. Early Stage Breast Cancer Lumpectomy Advantages • Local control and cosmesis are good/excellent in 90-95% of patients • Bar is set very high
  5. 5. • Minimally invasive or non-invasive therapy • Precise; real-time image guidance • Ambulatory, single session procedure • Local anesthesia or conscious sedation • Minimal post-procedure discomfort, rapid recovery, minimal scarring • Extremely low morbidity • ?Less expensive • ?Better patient satisfaction • ?Effective ABLATION OF BREAST CANCER
  6. 6. Ablation of Breast Cancer • Focused Microwave Thermotherapy • Chemical Ablation • Focused ultrasound ablation – Ultrasound guidance – MRI guidance • Cryoablation • Laser Ablation
  7. 7. Focused Ultrasound Ablation FUSA • Breast Diagnostic Ultrasound 7.5-15 MHz; sound waves reflected and “translated” into an image • Focused US for ablation 0.8 – 3.5 MHz; sound waves focused at the tumor site; noninvasive • Ablation caused by rapidly heating and physically disrupting the tumor due to the thermal energy generated by the sound waves • Tissue temperature 50-90o C; treatment time 35- 150 min depending on tumor size • Rate of temperature change and target temperature / volume treated can be controlled
  8. 8. FOCUSED ULTRASOUND ABLATION US guided or MRI guided Perpendicular to the Beam Path Parallel to the Beam Path Courtesy Dr. David Brenin
  9. 9. • Vast majority of studies have been done by a single investigator in China – less precise; insertion of probe is required for temperature mapping • 22 patients with T1 or T2 breast cancer – US-G FUSA with no excision – Followed with Mammo, US, MRI – 55 months follow-up • 2/22 (9%) local recurrence US-GUIDED FUSA Wu, et al Breast CA Res. And Treatment 2005, 92: 51-60
  10. 10. MRI-GUIDED FUSA • Non-invasive therapy – no probe • Real time monitoring by MRI – treatment – temperature
  11. 11. MR-G FUSA PLANNING STAGE Courtesy Dr. David Brenin
  12. 12. MRI-GUIDED FOCUSED ULTRASOUND ABLATION OF BREAST CANCER Courtesy Dr. David Brenin
  13. 13. • Gianfelice et al, J Vasc Interv Radiol 2003; 14:1275-1282 – 24 breast cancer pts high surgical risk or refused surgery – MR-G FUSA + Tamoxifen, mean follow up 20 months – 19/24 (79%) neg. core biopsy at 6 months – 1/24 (4%) second degree burn • Furusawa, et al. Breast Cancer 2007: 14:55-58 – 30 pts, tumor < 3.5cm; 25 evaluable pts – distance to skin surface > 1cm – IV sedation and analgesia – excision 5 to 23 days post-ablation – 60% of pts had 100% tumor necrosis; only 1 pt <95% necrosis – 1/25 (4%)skin burn, excised at surgery MR-G FUSA Feasibility Studies
  14. 14. Thermal coagulation Red zone: Edema, Inflammation Furusawa, et al J Am Coll Surg;203:54, 2006 MR-G FUSA PATHOLOGY
  15. 15. Inclusion criteria • Tumor size ≤ 1.5cm, well demarcated on MRI • Definitive diagnosis by core biopsy, negative SLNB • Skin-tumor distance ≥ 1.0 cm Study Design • Post-ablation core needle biopsy under US guidance within 3 weeks of treatment • Post ablation radiotherapy (whole breast + boost) • Follow-up MRI q 3-6 months MR-G FUSA EXCISIONLESS STUDY Furusawa 2010
  16. 16. MR-G FUSA EXCISIONLESS STUDY Furusawa 2010 Results • 47pts, 1.1cm mean tumor size • Mean treatment duration: 108 min. (65 - 209) • Mean f/u 43 months • No significant adverse events • No local recurrences
  17. 17. Courtesy of Breastopia Namba Hospital, Miyazaki, Japan Pre-Treatment T1w+c Post-Treatment T1w+c 18M FU T1w+c 30M FU T1w+c MR-G FUSA, EXCISIONLESS STUDY
  18. 18. MR-G FUSA EXCISIONLESS STUDY COSMESIS
  19. 19. ACRIN 6674/InSightec BC005 Awaiting final FDA approval •Phase II, multi-center, single arm study of pts with clinical T1N0 – Initial approval for 30 pts, then 220 pts – MR-G FUSA – MRI 10 – 14 days later – Excision Courtesy Dr. David Brenin
  20. 20. Cryoablation Courtesy Sanarus Technologies LLC
  21. 21. Cryoablation • Unique due to minimal, visibility of treatment zone under ultrasound –office procedure • FDA-cleared treatment (since 2004) for fibroadenomas • 3 mechanisms of cell damage and death • Intracellular ice formation • Extracellular osmotic imbalance, cell lysis upon thawing • Blood vessel damage and ischemia
  22. 22. Cryoablation • Monitored under real-time ultrasound guidance • Liquid nitrogen used for cooling • Probe is insulated • Initial swelling of treatment area • Tumor is replaced by organized necrotic debris • Gradual reabsorption / reorganization – fibrosis, hyalinization, fat necrosis
  23. 23. Cryoablation of Fibroadenomas Results - Clinical Data Overview 12-Month Outcomes 2004 Edwards, et al. (n=310 FA Tx) 12-Month Outcomes 2004 Kaufman, et al. (n=70 FA Tx) 12-Month Outcomes 2005 Nurko, et al. (n=444 FA Tx) 2.6 Year Outcomes 2005 Kaufman, et al. (n=32 FA Tx) Safety Profile Ecchymosis Hematoma Infections 41% 4.0% 2.0% Mild 3.0% NR NR NR NR NR NR NR U/S Volume Reduction 97% (n=12) 89% (n=57) 71% completely resolved (n=71) 99% (n=32) Non-Palpability (6 mo/12 mo) 50%/67% (n=89/12) NR/75% (n=NR/57) 54%/65% (n=237/82) 84% (n=27) Patient Satisfaction 90%/100% (6 mo /12 mo) (n=89/12) NR/91% (6 mo /12 mo) (n=NR/57) 91%/88% (6 mo /12 mo) (n=235/84) 97% 2.6 years (n=32) Well Tolerated Yes Yes Yes NA Patient Cosmesis Superior (6 mo & 12 mo) Good to Excellent (6 mo & 12 mo) Excellent (6 mo & 12 mo) 100% Satisfied 2.6 years
  24. 24. Cryoablation of Fibroadenomas Ultrasound Appearance
  25. 25. Cryoablation Courtesy Sanarus Technologies LLC
  26. 26. Cryoablation of Fibroadenomas Results
  27. 27. Cryoablation of Fibroadenomas Results
  28. 28. Cryoablation of Fibroadenomas Results
  29. 29. Cryoablation for Breast Cancer • Several small series, anecdotal reports • Sabel, et al Ann Surg Oncology 2004 11(5): 542-549 • 39 patients • 100% of cancers <1cm destroyed • Destruction of tumors 1-1.5cm if no EIC • Noncalcified DCIS cause of most failures
  30. 30. ACOSOG Z1072 • Primary Objectives: To determine the rate of complete tumor ablation in patients treated with cryoablation • Secondary Objectives: Negative predictive value of MRI post-ablation, Adverse events, Pain assessment, Technical factors affecting success Target accrual 99 patients Surgeon, pathologist and radiologist must be credentialed by ACOSOG – cryoablation experience, MRI review
  31. 31. ACOSOG Z1072 Rache Simmons, MD, FACS - PI Phase II Trial Evaluating the Efficacy of Pre and Post Treatment Imaging to Determine Residual Disease in Patients with Invasive Breast Carcinoma Undergoing Cryoablation Therapy Surgical resection Imaging (breast MR) Ablation therapy ( cryoablation) Imaging ( Mammography, US, Breast MR) Core biopsy for diagnosis including ER/PR, HER-2/neu, oncotype Invasive Ductal Breast Cancer (tumor ≤2cm)
  32. 32. ACOSOG Z1072 Tumor Imaging
  33. 33. ACOSOG Z1072 Probe placement and ablation
  34. 34. ACOSOG Z1072 MRI Appearance
  35. 35. ACOSOG Z1072 Pathology
  36. 36. S09-15441
  37. 37. Immune Response to Cryoablation Cryoablation-induced immune response demonstrated which inhibits the growth of metastatic foci Increase in anti-tumor T-Cells found in tumor draining lymph nodes after ablation Sabel Ann Surg Oncology 2010 Sabel Cryobiology 2006;53:360-366. Sabel Br Ca Res and Treatment 2005 90:97-104 Ablin RJ Arch Surg. 1998;133:106. Suzuki Y. Skin Cancer. 1995;10:19-26. Tanaka S. Cryobiology 1982;19:247-262.
  38. 38. ACOSOG 1072 • Rache Simmons, MD, FACS - PI • Currently 14 sites IRB-approved • 76 patients treated; target accrual 99 • Interim analysis at 50 patients – favorable to continue study
  39. 39. The Future?? • Core biopsy with genomic profiling; predictive of nodal status? • Studies are early, but promising • Need more data on: – local failure rates – cosmesis – cost effectiveness – patient satisfaction
  40. 40. • Likely to become procedure of choice if proven to have same or better local control rates – Patients will demand it – Surgeons should provide it NON-SURGICAL ABLATION OF BREAST CANCER
  41. 41. Breast Cancer Treatment Progress
  42. 42. References • Brenin, DR Focused Ultrasound Ablation for the Treatment of Breast Cancer Annals of Surgical Oncology (2011) 18:3088-3094 • Whitworth, P W, and Rewcastle, J C Cryoablation and Cryolocalization in the Management of Breast Disease Journal of Surgical Oncology (2005) 90:1–9 • Sabel, MS, Su, G, Griffith, KA, and Chang, AE Rate of Freeze Alters the Immunologic Response After Cryoablation of Breast Cancer Journal of Surgical Oncology (2005) 17:1187-1193 • Huston, TL, and Simmons, RM Ablative therapies for the treatment of malignant diseases of the breast The American Journal of Surgery 189 (2005) 694–701 • Sabel, MS, Kaufman,CS, Whitworth, P, Chang, H, Stocks, LH, Simmons, R, and Schultz,M Cryoablation of Early-Stage Breast Cancer: Work-in-Progress Report of a Multi-Institutional Trial Annals of Surgical Oncology 11(5):542–549 • Littrup, PJ, Jallad, B, Chandiwala-Mody, P, D’Agostini, M, Adam, BA, and Bouwman, D Cryotherapy for Breast Cancer: A Feasibility Study without Excision J Vasc Interv Radiol (2009) 20:1329–1341 • Tatli, S, Acar, M, Tuncali, K, Morrison, PR, and Silverman, S Percutaneous cryoablation techniques and clinical applications Diagn Interv Radiol 2010; 16:90–95 • Giuliano, AE, Hunt, KK, Ballman, KV, Beitsch, PD, Whitworth, PW, Blumencranz, PW, Leitch, AM, Saha, S, McCall, LM, and Morrow, M Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis - A Randomized Clinical Trial JAMA (2011) 305(6):569-575. • Kaufman, CS and Rewcastle, JC Cryosurgery For Breast Cancer Technology in Cancer Research and Treatment 2004 Apr; 3 (2) 165 – 175

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