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Clinical Trial
. 2009 Oct;20(10):1329-41.
doi: 10.1016/j.jvir.2009.06.029.

Cryotherapy for breast cancer: a feasibility study without excision

Peter J Littrup  1 , Bassel Jallad, Priti Chandiwala-Mody, Monica D'Agostini, Barbara A Adam, David Bouwman
Affiliations
Clinical Trial

Cryotherapy for breast cancer: a feasibility study without excision

Peter J Littrup et al. J Vasc Interv Radiol. 2009 Oct.

Abstract

Purpose: To assess the feasibility of percutaneous multiprobe breast cryoablation (BC) for diverse presentations of cancers that remained in situ after BC.

Materials and methods: After breast magnetic resonance (MR) imaging and thorough consultation, patients underwent BC after giving informed consent. This study was approved by the institutional review board. In 12 BC sessions, 22 breast cancer foci (stages I-IV) were treated in 11 patients who refused surgery by using multiple 2.4-mm cryoprobes. Five patients had recurrent disease and six had new diagnoses. With use of only local anesthesia, six patients were treated with ultrasonographic (US) guidance and five were treated with both computed tomographic (CT) and US guidance. Saline injections and warming bags were used to protect the skin. Procedure success was defined as 1 cm visible ice beyond all tumor margins. MR imaging and/or clinical follow-up were available for up to 72 months after BC.

Results: US produced sufficient ice visualization for small tumors, whereas CT helped confirm overall ice extent. The mean pretreatment breast tumor diameter was 1.7 cm +/- 1.2 (range, 0.5-5.8 cm), and an average of 3.1 cryoprobes produced 100% procedural success with mean ice diameters of 5.1 cm +/- 2.2 (range, 2.0-10.0 cm). No significant complications, retraction, or scarring were noted. Biopsies at the margins of the cryoablation site immediately after BC and at follow-up were all negative. No local recurrences have been noted at an average imaging follow-up of 18 months.

Conclusions: In conjunction with thorough pre- and postablation MR imaging, CT/US-guided multiprobe BC safely achieved 1 cm visible ice beyond tumor margins with minimal discomfort, good cosmesis, and no short-term local tumor recurrences.

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Conflict of interest statement

None of the other authors have identified a conflict of interest.

Figures

Figure 1
Figure 1
(a) Diagram shows basic isotherms for single and double cryoprobes. Accurate central placement of a single 2.4-mm cryoprobe (left image, arrow) within a simulated 1.2 × 1.2-cm tumor (dark gray) may still not produce sufficient lethal ice to cover all tumor margins (dashed line ~ <−30°C, diameter ~ 1.2 cm). Even though visible ice (solid outer line) may appear to cover all tumor margins, slight off-center placement (middle image, arrow) leaves grossly untreated tumor (bracket) beyond the lethal isotherm (dashed line). Tumor on right is covered by lethal ice due to synergy produced by two cryoprobes (15). (b) Avoiding posterior positive margins: heat load effects of the chest wall. The estimated temperature difference between skin surface (30°C) and chest wall/body (36°C) causes greater heat load along the posterior margin of ice propagation, which narrows the posterior distance between the visible (0°C) and lethal (–30°C) isotherms (curved solid arrows). Ablation on left shows central position of cryoprobes and greater anterior extension of visible ice beyond tumor margin; however, incomplete coverage of posterior tumor margins (black dashed arrows) is noted, similar to that seen in prior series (–26). Ablation on right shows through tumor coverage by lethal ice due to more posterior placement of cryoprobes in tumor (white straight arrows), thus overcoming heat-sink effect along the chest wall.
Figure 2
Figure 2
(a) US- guided cryotherapy for local control. Left image, BC performed with two cryoprobes (curved arrow) and a thermocouple (straight arrow) for an irregular 2.0-cm mass using technique planning noted in Figure 1b for tumors closer to the chest wall. As this was our second patient, this procedure also highlighted the need for better circumferential posterior visualization of the iceball near the chest wall, which was better provided with CT guidance. Middle image, Axial US image through the largest portion of the irregular mass shows more posterior placements of cryotherapy probes (curved arrows) and cross-section of a thermocouple en route to the superior tumor (straight arrow). Despite the cancer being near the chest wall, its medial location gave it a relatively superficial position for good US visualization. Right image, sagittal US image shows the posterior course of a thermocouple, which measured −57°C after ~8 minutes of the second freeze cycle at the superior tumor margin. The mobile nature of this tumor allowed substantial retraction off the chest wall in addition to saline injection. (b) MR images obtained before and four weeks after cryotherapy for local control. Left image, axial T1-weighted MR image obtained before cryotherapy at a similar tumor level as in Figure 2a. The tumor is causing retraction but does not involve the skin. Right image, MR image obtained four weeks after cryotherapy shows a low-signal-intensity rim of edema (black arrows) surrounding an ovoid zone of avascular necrosis that extended approximately 1 cm beyond all visible tumor margins but without extension into the chest wall. The wheelchair-bound patient, who was not a candidate for surgery, continued to do well with tumor involution of the primary and no further progression of distant metastases on anastrozole (Arimidex; AstraZeneca Pharmaceuticals, Delaware City, Delaware) alone until her death two years later.
Figure 3
Figure 3
(a) CT guidance before and after cryotherapy. Top images, unenhanced CT images at the level of the nipple and superior breast show extensive tumor involvement (T). The skin and tumor appear inseparable but were NOT fixed at physical examination or involved at US or MR imaging (Fig 5b). Middle images, CT images at the same levels immediately after cryotherapy and probe removal, leaving air in tracts. The tumors are covered by hypodense ice, except for the image on right, where the ice had already melted after cryoprobes had been retracted from an earlier medial freeze cycle. The saline injection needle remains between the tumor and the implant and skin had also been infiltrated. Bottom images, CT images obtained at the same anatomic levels 15 months after cryotherapy show marked resolution of prior bulky tumors. Random biopsies performed six weeks after ablation showed no residual tumor (T), but cancer recurred in two sites beyond the ablation zone at seven months. Repeat cryotherapy was done for a 6-mm new nodule in the far upper central breast and a 17-mm lower axillary node. (b) MR evaluation before (Pre) and 15 months after (Post) cryotherapy. Top images, before cryotherapy, T1-weighted fat-suppressed gadolinium-enhanced axial MR images show brisk enhancement throughout the tumor nodularity of the retroareolar (left) and superior (right) breast. Note also the lack of skin enhancement. Bottom images, T1-weighted fat-suppressed gadolinium-enhanced MR images obtained at the same levels 15 months after cryotherapy show a marked reduction of prior bulky tumors and no residual enhancement of any margin (arrows).
Figure 4
Figure 4
(a) MR images obtained before (Pre) and six weeks after (Post) cryotherapy of multifocal left upper outer quadrant cancer. Left image, T1-weighted axial image shows the spiculated, 1.6-cm dominant mass in the left outer quadrant (arrow). Another biopsy-confirmed cancer in the same quadrant was seen in different image planes. Middle image, fat-subtracted T1-weighted image obtained after the administration of gadolinium shows brisk tumor enhancement. Right image, T1-weighted, fat-subtracted, gadolinium-enhanced MR image obtained six weeks after cryotherapy shows a rim of enhancement corresponding to a healing cryotherapy rim, which also covered the other cancer. The microlumpectomy sampling (ie, Mammotome removal) of the tumor region before initiation of the freeze made our first BC procedure more complex. US visualization of the tumor site became distorted by blood during the vacuum-assisted biopsies, which are no longer used. Despite poor visualization of any remaining tumor margin, thorough ablation margins were still achieved by placing the cryoprobes along the outer margins of these microlumpectomy sites. Biopsy of three slightly nodular areas of rim enhancement showed no residual cancer or DCIS. (b) Images obtained at five-year follow-up. Top left image, T1-weighted axial MR image shows minimal scarring and/or distortion at the cryosite (arrow). Slightly smaller left breast was initially present and lateral scar indentation (arrowhead) is a scar from abscess débridement performed one year before this study (ie, four years after cryotherapy), which also confirmed no residual tumor throughout the original cryotherapy site. Bottom left image, T1-weighted fat-subtracted, gadolinium-enhanced MR image shows no enhancement of the previous ablation and subsequent resection sites (arrow). Right image, compression mammogram of the left upper outer quadrant shows no mass effect and minimal scarring, likely related to resection one year ago rather than original cryotherapy five years ago.
Figure 5
Figure 5
(a) Chest wall cryotherapy for bone metastasis about to break through skin. The patient was a 68-year-old woman with continuously growing sternal and soft tissue tumor but was otherwise stable. Results of positron emission tomography (PET) were negative for bone metastases from breast cancer. There was only a very thin layer of intact movable skin overlying the tumor. The top axial images show the 4.7 × 3.8 × 4.0-cm enhancing tumor (arrow), then covered in ice (arrowheads) extending to the skin surface. Bottom row shows sagittal reconstructions before (left) and during cryotherapy (middle), noting tumor (black arrows) covered by ice and warmed saline bags on skin (stars). Bottom right procedure image shows four cryoprobes and two skin injection sites. (b) Chest wall cryotherapy—follow-up. The hypovascular zone one month after BC (top row, arrowheads) corresponded to the visible ice extent 1 cm beyond the lateral tumor margins. Enhanced axial and coronal CT images obtained 18 months after BC (bottom row) show near-complete resorption of tumor mass with good remodeling of adjacent normal tissues (arrowheads). This area also remained negative at PET and bone scanning performed at 36 months, with no other distant disease recurrences.
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