Cryotherapy for a spectrum of breast
cancer: US and CT-guidance.
Peter J. Littrup, M.D.1*
Bassel Jallad, M.D.1
Priti Chandiwala-Mody, D.O.2
Monica D’Agostini1
Barb Adam, N.P.1
David Bouwman, M.D.3
1 Karmanos
Cancer Institute
2Department of Radiology, Wayne State University
3Department of Surgery, Wayne State University
* Co- Inventor/Founder: Single Phase Liquid Cooling (SPLC) by CryoMedix, LLC
Goals & Hypothesis
 To assess the technical feasibility, patient
acceptance, imaging and clinical outcomes of
percutaneous cryotherapy for breast cancers.
 Multiprobe cryoablation for diverse presentations
of breast cancer can be monitored to create 1cm
visible ice coverage beyond all tumor margins,
resulting in thorough cytotoxic coverage.
Introduction:
 Current treatments for LOCAL Breast Cancer
include surgery, radiation and/or chemotherapy
 Breast Conservation is the primary research focus
for new treatment options.
 Cryotherapy works by delivering lethal cold to ANY
cell ~ -30 0C x 2 cycles
 Benefits of Cryo?
– Much lower pain than heat-based ablations
– Easily visualized on CT/US/MR
– Excellent Healing ~ Eliminates disfiguring surgery
Introduction:
Breast Cryotherapy Research: Single probe
 Cryotherapy-assisted lumpectomy
–Tafra, et al. Ann Surg Oncol. 2003; 10:1018 –1024
 Excisional data
–Pfleiderer , et al. Invest Radiol. 2005; 40:472-477
–Roubidoux , et al. Imaging: Radiology. 2004; 233:857-867
 Conclusions:
– 100% kill for all tumors <1 cm & 1-1.5 cm with no DCIS
– Unreliable kill for tumors > 1.5 cm
– Incomplete along POSTERIOR margins
Materials and Methods:
Littrup et al., Lethal Isotherms of Cryoablation in a Phantom Study: Effects of Heat
Load, Probe Size, and Number JVIR 2009; 20:1343-1351
Cryotherapy for breast cancer: A feasibility study without excision.
J Vasc Interv Radiol 2009; 20:1329–1341.
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Minimum of 2 probes needed to cover 1cm tumor with lethal ice (< -30°C isotherm)
Multiple probes increase lethal ice: Surface area = 55% - 4 probes, 18% - 1 probe
• Multiple probes and/or
• Longer freeze times
correct for:
- higher heat loads
- lower probe power
Materials & Methods:
Patients - Procedures
 Informed consent included thorough counseling that cryo was
NOT standard of care, esp for newly dx potentially curative
 14 patients with 27 cancer foci of newly dx or recurrent breast
cancer were treated using US and/or CT-guidance
 Saline injections interposed between the developing ice ball
and the skin or chest wall for further thermal protection.
 Biopsy performed at ice margins immediately after procedure.
 CT and MRIs were performed in CA patients at available
follow-up times, up to 6 years post-procedure.
Materials & Methods:
Equipment
Results:
Locally Advanced Breast Cancer
Littrup PJ, et al. JVIR 2009
Results:
Locally Advanced Breast Cancer
Littrup PJ, et al. JVIR 2009
Results: Newly Dx Breast Cancer
Littrup PJ, et al. JVIR 2009
Five-year
Results:
Locally Advanced BCa & Implants
Littrup PJ, et al. JVIR 2009
Cryotherapy for BrCA: Local Recurrence
Littrup PJ, et al. JVIR 2009
Pre
1 mo.
18 mo.
Immediate
Results:
Patient
 Clinical difference – no resection!
 14 patients:
– 7 Locally advanced – on chemo/hormonal tx
 One had implants – froze into without damage
– 7 Intent to cure – multifocal + XRT/hormonal
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Total tumors – 27
Average tumor size – 1.7+ 1.2 cm (range: 0.5-5.8)
Minimal distortion – 80-90% resorption 6-12 mo.
No localized recurrences
– One regional recurrence in breast/axilla
Results:
Procedure
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Average cryoprobes - 3.2
Average ablation size – 51 mm
MR planning and follow-up crucial
Guidance – 8/14 pts CT and US; 6/14 US only
US/CT-guidance superb - operator dependent
No complications
Minimal discomfort - entirely outpatient
Able to address axillary nodes – nerves
Future of Breast Cryotherapy: MR-compatibility
Single Phase Liquid Cooling (SPLC)*
*CryoMedix, LLC
Vascular/Endoscopic
10 Sec
20 Sec
1 Min
2 Min
20 Thaw
MR - Compatibility
MR-monitored breast CA: Cadaver
Sagittal (left) and axial views of MR-compatible 1.5 mm cryoprobes at ~1.2mm apart,
generating immediate "cold" ice with minimal signal which then thaws over time (right),
(sharp initial margins, as well as greater T2 signal with thawing at 15 minutes).
Conclusions
 Ensure cytotoxic coverage - multiple probes
 Minimal pain
 Cosmetic satisfaction – implants OK, breast
conservation method
 Locally curative, control disease process
 Future: FDA trial with more patients and use
of new MRI compatible cryotechnology
(operator independence) is being planned
Thank You!