Ablative Therapy for Breast Cancer

Ablative Therapy for Breast Cancer American Society of Breast Surgeons

Annual Meeting Phoenix 2012

Disclosure

Consultant: IceCure Medical

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!

Early Stage Breast CancerLumpectomy Advantages

• Local control and cosmesis are good/excellent in 90-95% of patients

• Bar is set very high

• 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

Ablation of Breast Cancer

• Focused Microwave Thermotherapy• Chemical Ablation

• Focused ultrasound ablation– Ultrasound guidance– MRI guidance

• Cryoablation

• Laser Ablation

Focused Ultrasound AblationFUSA

• 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

FOCUSED ULTRASOUND ABLATIONUS guided or MRI guided

Perpendicular to the Beam Path

Parallel to the Beam Path

Courtesy Dr. David Brenin

• 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

MRI-GUIDED FUSA

• Non-invasive therapy– no probe

• Real time monitoring by MRI– treatment– temperature

MR-G FUSA PLANNING STAGE

Courtesy Dr. David Brenin

MRI-GUIDED FOCUSED ULTRASOUND ABLATION OF BREAST CANCER

Courtesy Dr. David Brenin

• 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 FUSAFeasibility Studies

Thermal coagulation

Red zone: Edema, Inflammation

Furusawa, et al J Am Coll Surg;203:54, 2006

MR-G FUSA PATHOLOGY

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 STUDYFurusawa 2010

MR-G FUSA EXCISIONLESS STUDYFurusawa 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

Courtesy of Breastopia Namba Hospital, Miyazaki, Japan

Pre-TreatmentT1w+c

Post-TreatmentT1w+c

18M FUT1w+c

30M FUT1w+c

MR-G FUSA, EXCISIONLESS STUDY

MR-G FUSA EXCISIONLESS STUDY COSMESIS

ACRIN 6674/InSightec BC005Awaiting 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

Cryoablation

Courtesy Sanarus Technologies LLC

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

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

Cryoablation of FibroadenomasResults - Clinical Data

Overview12-Month Outcomes

2004Edwards, et al.(n=310 FA Tx)

12-Month Outcomes2004

Kaufman, et al.(n=70 FA Tx)

12-Month Outcomes2005

Nurko, et al.(n=444 FA Tx)

2.6 Year Outcomes2005

Kaufman, et al.(n=32 FA Tx)

Safety ProfileEcchymosisHematomaInfections

41% 4.0% 2.0%

Mild 3.0% NR

NRNRNR

NRNRNR

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% Satisfied2.6 years

Cryoablation of FibroadenomasUltrasound Appearance

Cryoablation

Courtesy Sanarus Technologies LLC

Cryoablation of FibroadenomasResults

Cryoablation of FibroadenomasResults

Cryoablation of FibroadenomasResults

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

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

ACOSOG Z1072Rache 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)

ACOSOG Z1072Tumor Imaging

ACOSOG Z1072Probe placement and ablation

ACOSOG Z1072MRI Appearance

ACOSOG Z1072Pathology

S09-15441

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.

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

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

• 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

Breast Cancer TreatmentProgress

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)

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