Cryotherapy for a spectrum of breast Cryotherapy for a spectrum of breast cancer: US and CT-guidance.cancer: US and CT-guidance.

Peter J. Littrup, M.D.Peter J. Littrup, M.D.1*1*

Bassel Jallad, M.D.Bassel Jallad, M.D.11

Priti Chandiwala-Mody, D.O.Priti Chandiwala-Mody, D.O.22

Monica D’AgostiniMonica D’Agostini11

Barb Adam, N.P.Barb Adam, N.P.11

David Bouwman, M.D.David Bouwman, M.D.33

1 1 Karmanos Cancer InstituteKarmanos Cancer Institute22Department of Radiology, Wayne State UniversityDepartment of Radiology, Wayne State University

33Department of Surgery, Wayne State UniversityDepartment of Surgery, Wayne State University

* Co- Inventor/Founder: Single Phase Liquid Cooling (SPLC) by CryoMedix, LLC* Co- Inventor/Founder: Single Phase Liquid Cooling (SPLC) by CryoMedix, LLC

Goals & Goals & HypothesisHypothesis

To assess the technical feasibility, patient To assess the technical feasibility, patient acceptance, imaging and clinical outcomes of acceptance, imaging and clinical outcomes of percutaneous cryotherapy for breast cancers. percutaneous cryotherapy for breast cancers.

Multiprobe cryoablation for diverse presentations Multiprobe cryoablation for diverse presentations of breast cancer can be monitored to create 1cm of breast cancer can be monitored to create 1cm visible ice coverage beyond all tumor margins, visible ice coverage beyond all tumor margins, resulting in thorough cytotoxic coverage.resulting in thorough cytotoxic coverage.

Introduction:Introduction: Current treatments for LOCAL Breast Cancer Current treatments for LOCAL Breast Cancer

include surgery, radiation and/or chemotherapyinclude surgery, radiation and/or chemotherapy Breast ConservationBreast Conservation is the primary research focus is the primary research focus

for new treatment options.for new treatment options.

Cryotherapy works by delivering Cryotherapy works by delivering lethallethal cold to ANY cold to ANY cell ~ -30 cell ~ -30 00C x 2 cyclesC x 2 cycles

Benefits of CryoBenefits of Cryo??– Much lower pain than heat-based ablationsMuch lower pain than heat-based ablations

– Easily visualized on CT/US/MREasily visualized on CT/US/MR

– Excellent HealingExcellent Healing ~ Eliminates disfiguring surgery ~ Eliminates disfiguring surgery

Introduction:Introduction:Breast Cryotherapy Research: Breast Cryotherapy Research: Single probeSingle probe

Cryotherapy-assisted lumpectomyCryotherapy-assisted lumpectomy

–TafraTafra, et al. Ann Surg Oncol. 2003; 10:1018 –1024, et al. Ann Surg Oncol. 2003; 10:1018 –1024

Excisional dataExcisional data

–Pfleiderer Pfleiderer , et al. Invest Radiol. 2005; 40:472-477, et al. Invest Radiol. 2005; 40:472-477

–Roubidoux Roubidoux , et al. Imaging: Radiology. 2004; 233:857-867, et al. Imaging: Radiology. 2004; 233:857-867

ConclusionsConclusions::

– 100% kill for all tumors <1 cm & 1-1.5 cm with no DCIS100% kill for all tumors <1 cm & 1-1.5 cm with no DCIS

– Unreliable kill for tumors > 1.5 cmUnreliable kill for tumors > 1.5 cm

– Incomplete along POSTERIOR marginsIncomplete along POSTERIOR margins

Materials and Methods:Materials and Methods:Littrup et al.,Littrup et al., Lethal Isotherms of Cryoablation in a Phantom Study: Effects of Heat Load, Lethal Isotherms of Cryoablation in a Phantom Study: Effects of Heat Load,

Probe Size, and Number JVIR 2009; 20:1343-1351Probe Size, and Number JVIR 2009; 20:1343-1351Cryotherapy for breast cancer: A feasibility study without excision. Cryotherapy for breast cancer: A feasibility study without excision.

J Vasc Interv Radiol 2009; 20:1329–1341.J Vasc Interv Radiol 2009; 20:1329–1341.

Minimum of 2 probes needed to cover 1cm tumor with lethal ice (< -30°C isotherm)Minimum of 2 probes needed to cover 1cm tumor with lethal ice (< -30°C isotherm)

Multiple probes increase lethal ice: Multiple probes increase lethal ice: Surface areaSurface area = 55% - 4 probes, 18% - 1 probe = 55% - 4 probes, 18% - 1 probe

• Multiple probes and/orMultiple probes and/or• Longer freeze timesLonger freeze times

correct for: correct for: - higher heat loads- higher heat loads- lower probe power- lower probe power

Materials & Methods: Materials & Methods: Patients - ProceduresPatients - Procedures

Informed consent included thorough counseling that cryo was Informed consent included thorough counseling that cryo was

NOT standard of care, esp for newly dx potentially curativeNOT standard of care, esp for newly dx potentially curative

14 patients with 27 cancer foci of newly dx or recurrent breast 14 patients with 27 cancer foci of newly dx or recurrent breast

cancer were treated using US and/or CT-guidance cancer were treated using US and/or CT-guidance

Saline injections interposed between the developing ice ball Saline injections interposed between the developing ice ball

and the skin or chest wall for further thermal protection. and the skin or chest wall for further thermal protection.

Biopsy performed at ice margins immediately after procedure.Biopsy performed at ice margins immediately after procedure.

CT and MRIs were performed in CA patients at available CT and MRIs were performed in CA patients at available

follow-up times, up to 6 years post-procedure.follow-up times, up to 6 years post-procedure.

Materials & Methods:Materials & Methods:EquipmentEquipment

Results:Results:Locally Advanced Breast CancerLocally Advanced Breast Cancer

Littrup PJ, et al. JVIR 2009Littrup PJ, et al. JVIR 2009

Results:Results:Locally Advanced Breast CancerLocally Advanced Breast Cancer

Littrup PJ, et al. JVIR 2009Littrup PJ, et al. JVIR 2009

Results:Results: Newly Dx Breast CancerNewly Dx Breast Cancer

Five-year

Littrup PJ, et al. JVIR 2009Littrup PJ, et al. JVIR 2009

Results:Results: Locally Advanced BCa & ImplantsLocally Advanced BCa & Implants

Littrup PJ, et al. JVIR 2009Littrup PJ, et al. JVIR 2009

Cryotherapy for BrCA: Local RecurrenceCryotherapy for BrCA: Local RecurrenceLittrup PJ, et al. JVIR 2009Littrup PJ, et al. JVIR 2009

PrePre Immediate Immediate

1 mo.1 mo.

18 mo. 18 mo.

Results:Results:PatientPatient

Clinical difference – no resection!Clinical difference – no resection! 14 patients:14 patients:

– 7 Locally advanced – on chemo/hormonal tx7 Locally advanced – on chemo/hormonal tx One had implants – froze into without damageOne had implants – froze into without damage

– 7 Intent to cure – multifocal + XRT/hormonal7 Intent to cure – multifocal + XRT/hormonal

Total tumors – 27Total tumors – 27 Average tumor size – 1.7Average tumor size – 1.7++ 1.2 cm (range: 0.5-5.8) 1.2 cm (range: 0.5-5.8) Minimal distortion – 80-90% resorption 6-12 mo.Minimal distortion – 80-90% resorption 6-12 mo. No localized recurrencesNo localized recurrences

– One regional recurrence in breast/axillaOne regional recurrence in breast/axilla

Results:Results: ProcedureProcedure

Average cryoprobes - 3.2Average cryoprobes - 3.2 Average ablation size – 51 mmAverage ablation size – 51 mm MR planning and follow-up crucialMR planning and follow-up crucial Guidance – 8/14 pts CT and US; 6/14 US onlyGuidance – 8/14 pts CT and US; 6/14 US only US/CT-guidance superb - operator dependentUS/CT-guidance superb - operator dependent No complicationsNo complications Minimal discomfort - entirely outpatientMinimal discomfort - entirely outpatient Able to address axillary nodes – nervesAble to address axillary nodes – nerves

Future of Breast CryotherapyFuture of Breast Cryotherapy: MR-compatibility: MR-compatibility Single Phase Liquid Cooling (SPLC)*Single Phase Liquid Cooling (SPLC)*

*CryoMedix, LLC*CryoMedix, LLC

Vascular/EndoscopicVascular/Endoscopic

10 Sec10 Sec 20 Sec20 Sec 1 Min1 Min 2 Min2 Min 20 Thaw20 Thaw

MR - CompatibilityMR - Compatibility

MR-monitored breast CAMR-monitored breast CA:: CadaverCadaverSagittal (left) and axial views of MR-compatible 1.5 mm cryoprobes at ~1.2mm apart, 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), 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). (sharp initial margins, as well as greater T2 signal with thawing at 15 minutes).

ConclusionsConclusions

Ensure cytotoxic coverage - multiple probesEnsure cytotoxic coverage - multiple probes

Minimal painMinimal pain

Cosmetic satisfaction – implants OK, breast Cosmetic satisfaction – implants OK, breast conservation methodconservation method

Locally curative, control disease processLocally curative, control disease process

Future: FDA trial with more patients and use Future: FDA trial with more patients and use of new MRI compatible cryotechnology of new MRI compatible cryotechnology (operator independence) is being planned (operator independence) is being planned

Thank You!Thank You!