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’Agostini 1 Barb Adam, N.P. 1 David Bouwman, M.D. 3 1 Karmanos Cancer Institute 2 Department of Radiology, Wayne State University 3 Department 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 ~ C 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: –Roubidoux, et al. Imaging: Radiology. 2004; 233:  Conclusions: – 100% kill for all tumors <1 cm & 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: Cryotherapy for breast cancer: A feasibility study without excision. J Vasc Interv Radiol 2009; 20:1329–1341.  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/orMultiple probes and/or Longer freeze timesLonger 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 Five-year Littrup PJ, et al. JVIR 2009

Results: Locally Advanced BCa & Implants Littrup PJ, et al. JVIR 2009

Cryotherapy for BrCA: Local Recurrence Littrup PJ, et al. JVIR 2009 PreImmediate 1 mo. 18 mo.

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  Total tumors – 27  Average tumor size – cm (range: )  Minimal distortion – 80-90% resorption 6-12 mo.  No localized recurrences –One regional recurrence in breast/axilla

Results: Procedure  Average cryoprobes  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!