Cryoablation of Breast Cancer: Clinical & Imaging Follow-up of Nonresected Invasive Carcinoma
Jennifer Thiel Bergin, MD Gale A Sisney, MD Elizabeth S Burnside, MD Lonie R Salkowski, MD University of Wisconsin Hospital & Clinics
Objectives
Review the use of cryoablation in benign breast disease Review the current data regarding the use of cryoablation in malignant breast disease Present a case of ablated, unresected breast cancer & illustrate the imaging changes over time
Disclosures
This exhibit describes a non-FDA approved use of cryoablation in the treatment of breast cancer The authors have no sponsorships, partnerships, or royalties to disclose.
Outline
Introduction to cryoablation
How it works
Review of literature Review of published data A case of ablated, unresected breast cancer
Cryoablation of benign tumors
Cryoablation of malignant tumors
UW Breast Center experience
Summary and future directions
Introduction to Cryoablation
What is Cryoablation?
Cell destruction using cold temperatures
How it works
Joule Thompson principle is utilized to alter temperatures in the cryoprobe Argon cools when it expands in the probe tip & freezes tissue Helium warms when it expands & thaws
Cryoablation technology (JouleThompson principle)
atmosphere Expansion chamber
High pressure argon
Cryoprobe
-160° C
Courtesy Fred T. Lee
How cryoablation kills
1. Intracellular ice formation
2. Extracellular ice formation 3. Capillary endothelial damage
4. Immunologic effect
- unique to cryoablation:
The results
Thrombosis
Clean demarcation between living and dead tissue
Courtesy Fred T. Lee
Cryoablation of Benign Tumors
Benign breast tumors
Fibroadenomas Young, healthy females BI-RADS 4a 1.4 million needle biopsies annually 1 million benign lesions diagnosed
Benign breast tumors
500,000 fibroadenomas excised annually Factors leading to excision
Palpable prominence Discomfort Growth Peace of mind
Cryoablation in benign breast tumors
Littrup et al.
2004
Performed cryoablation on biopsy proven benign lesions
Outpatient setting Local anesthesia No sedation
Littrup et al.
78 lesions treated
Average tumor size 2.0 cm (0.7-4.2cm) If needed, saline injected for skin & chest wall protection
No minimum distance from the skin
Littrup et al.
Double freeze thaw cycle
Freeze times determined by tumor size
Results
Virtually painless Excellent cosmetic results
Scars resolved in most by 3 months 80% non-palpable at 6 months
Palpable satisfaction
Cost-effective
Post ablation appearance
Mammography
No interfering artifacts on mammography
Gradual resorption with minimal residual density & no calcifications
Ultrasound
Oval accumulation of hypoechoic necrotic debris Ill-defined borders Occasional shadowing
Mammogram changes
Pre ablation
12 months post ablation
Courtesy Peter J Littrup
Ultrasound changes
Pre Immediately Post
1 week
3 month
Courtesy Peter J Littrup
Littrup’s conclusion
Ultrasound guided cryoablation is safe and effective for benign breast lesions Littrup PJ, Freeman-Gibb L, Andea A, White M, et al. Cryotherapy for breast fibroadenomas. Radiology 2005; 234:6372.
Cryoablation of Malignant Tumors
Malignant breast tumors
211,000 estimated new cases of invasive cancer in 2005 58,000 estimated new in situ cases 40,000 deaths attributable to breast cancer
Size of tumor at detection
3 2.5
2
Size (cm)
1.5
Size (cm)
1
0.5
0 1965
1970
1975
1980
1985 Year
1990
1995
2000
2005
Adapted from Kaufman CS, Cryoablation – The next advance in breast cancer care? Bus Brief: Global Surg, 2005.
Size of tumor at detection
Goal: 50% of newly diagnosed breast cancers will be <1cm by 2010
Evolution of treatment
Nothing Radical mastectomy Modified mastectomy Lumpectomy + whole breast irradiation Lumpectomy + partial breast irradiation
Standard of care 2007
Lumpectomy with radiation therapy Sentinel node mapping Chemotherapy Chemoprevention
Evolution of treatment
The next step: ablation + partial breast irradiation ?
Potential advantages of cryoablation
Office based treatment No IV anesthesia needed Shorter recovery Likely lower total cost Patient satisfaction Cosmesis Imaged lesions expected to resorb over time without increased scar formation Possible immunologic effects
Cryoablation of malignant breast tumors
Staren and Sabel
1997 2002, 2005 (Europe) 2004 (University of Michigan, Department of Surgery) First prospective, multiinstitutional trial
Pfleiderer et al.
Sabel et al.
Sabel et al.
Performed cryoablation on 27 patients with tumors <1.8 cm
Resected tumors 6-30 days after cryo
Sabel et al.
Results
Tumors <1 cm were fully ablated Tumors 1 to 1.5 cm without an extensive intraductal component were fully ablated Tumors >1.5 cm NOT reliably fully ablated
Sabel et al.
Conclusion
Cryoablation of primary breast cancers is safe and effective, but should be limited to invasive carcinomas <1.5 cm with <25% DCIS on the core biopsy.
UW Breast Center Experience
Cryoablation without resection
Our patient…. 85-year-old with invasive ductal carcinoma
two <1.0cm foci refused surgical treatment refused radiation therapy refused chemotherapy or chemoprevention refused resection
Diagnostic Mammogram, Pretreatment
4:00
2:00
UW Cryoablation patient
Ultrasound guided core biopsy x 2 4:00 lesion: Invasive ductal carcinoma, grade 2 2:00 lesion: Invasive ductal carcinoma, grade 1 with low grade DCIS ER/PR positive
Pre-procedure lesion at 2:00
Pre-procedure lesion at 4:00
Patient prep
IV Pre-procedural antibiotics Midazolam 0.5mg, Fentanyl 50 mcg
Patient prep
Local anesthesia 3mm incision for probe placement
Cryoablation probe
Probe insertion
Cryoablation probe
Second probe placed
Cryoablation probes
Warm saline bag placed at probe entry for skin protection
Procedure
Short freezing cycle to secure probes 10 minute freeze cycle 5 minute passive thaw 10 minute freeze cycle Active thaw cycle
Cryoablation iceball monitoring
Cryoablation procedure 2:00
Cryoablation procedure 2:00
Cryoablation procedure 2:00
Cryoablation procedure 4:00
Cryoablation procedure 4:00
Cryoablation procedure 4:00
Iceballs at the end of ablation
Post procedure incision sites
2 hours post ablation
2 hours post ablation
6 week follow-up
2:00
4:00
6 week follow-up
6 week follow-up
6 week follow-up
3 month follow-up
3 month follow-up
3 month follow-up
3 month follow-up
6 month follow-up
6 month follow-up
6 month follow-up
6 month follow-up
Cosmetic appearance at 6 months
No visible scar!
UW Breast Center Experience
At 9 months, our patient is
Free of known disease Highly satisfied with the treatment
The changes we’ve seen on ultrasound & mammography are similar to those noted following ablation of benign breast disease
UW Breast Center Experience
What’s next for our patient?
Continued follow-up with mammogram & ultrasound Will biopsy if suspicious changes arise
Summary and Future Directions
Summary
Cryoablation is safe, effective, & FDA approved in the treatment of benign breast disease. Cryoablation should be considered in patients with benign breast disease
Summary
Cryoablation can safely & efficiently treat small breast cancers Cryoablation achieves 100% cell kill in small cancers without extensive DCIS
Summary
In our experience, cryoablation of breast cancer without resection is…
Technically feasible Well-tolerated
The post-ablation changes on imaging follow a pattern similar to that seen with benign breast tumors
No architectural distortion or calcification
Future directions
Further work needed
Patient selection Detection of multifocal noncalcified DCIS
Mammography sensitivity 40% MRI sensitivity 70%
Margin clearance Noninvasive determination of nodal status Cost analysis Immunologic effect