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PercutaneousCryoablationofSymptomaticExtraabdominalMetastaticDisease:PreliminaryResults

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Beland et al.Cryoablation of Extraabdominal Metastatic DiseaseCryoablation

Original Report

Michael D. Beland1 Damian E. Dupuy William W. Mayo-SmithBeland MD, Dupuhy DE, Mayo-Smith WW

Received March 4, 2004; accepted after revision June 14, 2004.

1All authors: Department of Diagnostic Imaging, BrownMedical School, Rhode Island Hospital, 593 Eddy St.,Providence, RI 02903. Address correspondence to D. E. Dupuy (ddupuy@lifespan.org).

Percutaneous Cryoablation of Symptomatic Extraabdominal Metastatic Disease: Preliminary Results

OBJECTIVE. The objective of our study was to describe our initial experience using per-cutaneous cryoablation for palliation of symptomatic extraabdominal metastases or recurrentsoft-tissue tumors.

CONCLUSION. Preliminary results suggest that percutaneous cryoablation may offer aminimally invasive alternative for relief of symptomatic metastatic disease in patients forwhom conventional therapy failed.

ntraoperative cryoablation of met-astatic disease has been well docu-mented in the liver [1]. Experiencewith percutaneous cryoablation

has been limited because of the large applica-tor diameter of the earlier systems and the as-sociated high incidence of postprocedurebleeding [2]. Percutaneous treatment of pros-tate cancer using sonographic guidance hasbeen described by several authors [3–5]. Withthe development of an argon-based system, ap-plicator diameters have decreased significantlyfrom 8 to 2.4 mm and made percutaneous utili-zation of this technique at other sites more fea-sible. Recent literature has been published onpercutaneous cryoablation of hepatic and renaltumors [6–8]. To our knowledge, experiencewith percutaneous cryoablation of recurrent ormetastatic disease outside the abdomen hasbeen very limited [9].

Recurrent local or metastatic disease to ex-traabdominal sites is a source of significantmorbidity. Symptoms include local pain andmass effect on adjacent structures. Surgicalresection of locally invasive disease is oftennot an option because of poorly defined mar-gins, involvement of adjacent critical struc-tures, inaccessible location, and comorbid

conditions. Long recovery time and compli-cations may also follow complicated surgicalresections. Percutaneous therapy potentiallyoffers these patients palliation and improvedquality of life with minimal recovery time.

Subjects and MethodsThis study was approved by the hospital institu-

tional review board. The four patients in this studyunderwent consultation with a staff radiologist be-fore booking the procedure and had normal resultson preprocedure coagulation studies (prothrombintime, partial thromboplastin time, internationalizednormalized ratio, platelet count). CT fluoroscopywas used for imaging guidance. Two patients re-ceived general anesthetic, and two had conscious se-dation using midazolam, fentanyl, and continuousmonitoring using dedicated nursing personnel ac-cording to our hospital’s protocol. The procedureswere performed at our institution over approxi-mately 2 months comprising approximately 10% ofour tumor ablation volume for that period of time.

CryoablationCryoablation was performed using an argon-

based cryoablation system (Endocare, Mountain-view) and 2.4-mm percutaneous applicators. The ap-plicators have a 5-cm active tip and create a freeze

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zone of approximately 5 × 1.5–2.0 cm (length ×width). Up to eight applicators were placed simulta-neously (range, 5–8 applicators) 2 cm apart in the pa-tient. Temperatures were measured during theprocedure with an attached thermocoupler (range, −94°C to −136°C). Placement was planned accordingto the size of the tumor and margin of the tumor andof destroyed bone to achieve pain palliation. Eachpatient underwent multiple 8- to 11-min freeze cy-cles, each followed by a 5-min active helium thaw.The low-density changes within the tissue were mea-sured to approximate the size of the ablated region.Visible treatment margins were routinely extended 1cm beyond the tumor during cryoablation. The terms“freeze zone,” “ice ball,” and “treatment area” areused interchangeably in the text and refer to the areaof decreased density visualized on CT after the tissuehas been frozen.

Patients and Treatment:The first patient was a 57-year-old man diag-

nosed with rectal cancer who underwent primaryresection and diverting colostomy (Table 1). Sevenyears later, he was diagnosed with local recurrencein the presacral region. Abdominoperoneal resec-tion and placement of a right distal ureteral stentwere performed followed by local radiation ther-apy. CT scans obtained 1 year later revealed an en-larging presacral mass and a chemotherapyregimen of irinotecan, 5-fluorouracil, and leucov-orin was initiated. The patient subsequently devel-oped two pulmonary metastases; each was treatedtwice with percutaneous radiofrequency ablation.Follow-up CT examination showed continued en-largement of the presacral mass with bony invasionand increased activity on PET.

The painful 9 × 5 × 7.5 cm mass was treated withCT-guided percutaneous cryoablation (Fig. 1) withthe patient under conscious sedation. Eight cryoap-plicators were placed into the mass, and two 10-minfreeze–thaw cycles were performed. A 10 × 5 × 7cm freeze zone was measured on CT performed im-mediately after treatment (Fig. 1B). The patientwas transferred to the recovery room in stable con-dition and discharged after 2 hr with no immediatecomplications. He reported immediate improve-ment in preprocedure pain. Twelve months after

treatment, he continues to have no pain and has notundergone follow-up imaging.

The second patient was a 20-year-old womanwith a nonosseous Ewing’s sarcoma arising fromthe soft tissues adjacent to the pubic symphysis (Ta-ble 1). The 12-cm tumor was surgically resectedwith no reported evidence of metastatic disease.The patient refused chemotherapy and radiationtherapy. Follow-up CT scans revealed no residualdisease until 4 years later when a local recurrencein the pelvis was documented by sonographicallyguided percutaneous biopsy. The patient again re-fused chemotherapy and radiation therapy. Shortlythereafter, she developed abdominal pain; weightloss; and right hydronephrosis, which was treatedwith ureteral stent placement. CT examination 28months later showed a 13 × 15 × 17 cm right pelvicmass with destructive changes in the right superiorpubic ramus and pubic symphysis.

The patient was referred to our department forpalliative CT-guided percutaneous cryoablation.With the patient under general anesthesia at her re-quest, seven cryoapplicators were placed into themass and an 11-min freeze–thaw cycle followed bya 5-min thaw was performed. The applicators werethen repositioned, and a second 8-min freeze–thawcycle was performed. The freeze zone was 8 × 12 ×6 cm on CT performed immediately after treatment.The patient was transferred to the recovery room instable condition. After 2 hr of uneventful observa-tion, she was transferred back to the medical floor fortreatment of preexisting anemia and pain. She re-ported that her pain was improved, and she was dis-charged 3 days after the procedure. Four weeks afterthe procedure, she was ambulating and had furtherimprovement in her pain. She died 1 month later.

The third patient was a 55-year-old woman diag-nosed with adenocarcinoma of the left breast (Table1). Modified radical mastectomy was performedwith negative resection margins, and three of 10 ax-illary lymph nodes were positive for malignancy.She then completed six cycles of chemotherapy withcyclophosphamide, methotrexate, and 5-fluorouraciland was placed on tamoxifen. She did well until 4years later when she developed a palpable lump inthe left supraclavicular region. Biopsy was positivefor metastatic adenocarcinoma, consistent with

breast origin. Surgical excision was performed fol-lowed by postoperative external beam radiation (to-tal dose, 60 Gy). Ten months later, she developed leftarm pain from a brachial plexopathy. Gadolinium-enhanced MRI depicted a 3 × 3 × 3 cm enhancingsoft-tissue mass deep in relation to the pectoralismuscle in the region of the left brachial plexus in thearea of recent radiation therapy (Fig. 2C). CT-guidedbiopsy confirmed metastatic adenocarcinoma.

Patient 3 was referred for palliative treatmentwith CT-guided percutaneous cryoablation (Fig. 2),which was performed while she was under con-scious sedation. The patient was advised that dam-age to the brachial plexus during treatment washighly likely, but she agreed to undergo the treat-ment because of the severe pain. Six cryoapplica-tors were placed into the mass, and two consecutive8-min freeze–thaw cycles were performed. The ap-plicators were repositioned, and a third 8-minfreeze–thaw cycle was performed. A freeze zone of7 × 5 × 6 cm was obtained (Fig. 2B). She was ob-served in the recovery area for 2 hr after the proce-dure. Before she was discharged, she reported animprovement in her left arm pain and some im-provement in motor function. At a follow-up officevisit, she had subsequently lost most motor func-tion and sensation in that arm but was essentiallypain-free. She was aware of this possibility beforethe procedure and was pleased with the treatmentoutcome. Follow-up MRI performed 7 weeks aftertreatment showed no change in tumor size with apersistent 1-cm area of enhancement surroundingthe left subclavian artery (Fig. 2D). She continuesto report no pain 13 months after cryoablation.

The fourth patient was a 49-year-old man withcolon cancer (Table 1). He underwent right hemi-colectomy and intraoperative radiofrequency abla-tion of a single 9-mm liver metastasis. He receivedfive cycles of chemotherapy with 5-fluorouracil,leucovorin, and irinotecan. One year later, he devel-oped pain in the medial posterior mid back and CTrevealed a 4 × 7 × 8 cm soft-tissue mass causingbony destruction of the posterior right 10th and11th ribs. Biopsy results indicated the mass wasmetastatic colon carcinoma. He was treated with ra-diation therapy (total dose, 50 Gy) and placed on achemotherapy regimen of five cycles of 5-fluorou-racil, leucovorin, and oxaliplatin. CT-guided percu-taneous radiofrequency ablation of the chest wallmass was performed 1 month later. He experienceda moderate amount of procedural pain, and thetreatment was terminated prematurely. Follow-upCT examination 6 months later showed an increasein size of the mass, now measuring 9 × 7.5 × 6 cm.

Because of the size of the lesion and the pain asso-ciated with the previous radiofrequency ablation, thepatient was treated with CT-guided percutaneous cryo-ablation under laryngeal mask anesthesia. Five cryoap-

TABLE 1 Cryoablation Data

Patient No. No. of Applications No. of Freeze Cycles Initial Tumor Size (cm) Tumor Ablation Size (cm)

1 8 2 9 × 5 × 7.5 10 × 5 × 7

2 7, 7a

aIndicates applicators were repositioned during additional treatment cycles.

2 13 × 15 × 17 8 × 12 × 6

3 6, 6a 3 3 × 3 × 3 7 × 5 × 6

4 5, 5a 4 9 × 7.5 × 6 9 × 8 × 8

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plicators were placed into the anterolateral componentof the mass, and two 8-min freeze–thaw cycles wereperformed. The probes were then repositioned into themedial aspect of the mass, and two 8-min freeze–thawcycles were repeated. A freeze zone of 9 × 8 × 8 cmwas obtained. The patient was transferred to the recov-ery room after the procedure and observed for 2 hr. Hewas discharged from the hospital with no immediate

complications. One week after the procedure, he re-ported improved tolerance of his pain, but he experi-enced a change in the quality of the preprocedure painthat required the addition of the analgesic gabapentinto his medical therapy for neuropathic pain. Despiteimprovement in pain tolerance, follow-up CT exami-nation 3.5 months after treatment showed an increasein the craniocaudal dimension to approximately 12 cm

with no change in the transverse or anteroposterior ex-tent. The patient underwent emergency thoracic lami-nectomy for decompression of metastatic disease 8months after treatment.

ResultsPercutaneous cryoablation was performed

in four patients with extraabdominal recurrent

Fig. 1.—57-year-old man with metastatic rectal cancer and local presacral recurrence.A, Prone noncontrast CT image obtained in transaxial plane shows large presacraltumor with bone destruction (arrows).B, Cryoablation was performed on recurrent presacral rectal cancer. Prone noncon-trast CT image obtained in transaxial plane shows round low-density area represent-ing volume of frozen tissue at end of second freeze cycle.C, Photograph of procedure shows cryoapplicator position under CT fluoroscopy.D, Axial 18FDG PET image obtained at level of presacral mass before treatment showsincreased activity consistent with metabolically active tumor (arrow).E, Axial 18FDG PET image obtained at same level as D 4 months after procedure showsphotopenic defect (arrow) in area of treatment, consistent with necrotic tumor.

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or metastatic cancer for whom surgical resec-tion, chemotherapy, or external beam radiationtherapy had failed. The treatments were per-formed over a period of approximately 2months. Three of the lesions were large enoughto require repositioning of the cryoapplicatorand repeat treatment. Eleven total freeze cycles

were performed on four lesions during four in-dividual patient treatment sessions.

All patients tolerated the procedure well.None of the patients developed significantbleeding or vascular injury. Nerve damage tothe brachial plexus did occur during treat-ment of the third patient. While this damage

may be considered a complication, it was anexpected outcome and was acceptable to thepatient.

All patients had follow-up office visits ortelephone contact (range, 2–13 months; me-dian, 12.5 months) and imaging as describedpreviously.

Fig. 2.—55-year-old woman with recurrent metastatic breast cancer to left supraclavicular region with infiltration of brachial plexus after failure of local excision, chemo-therapy, and radiation therapy.A, Contrast-enhanced supine transaxial CT scan obtained before treatment shows soft-tissue mass (arrows) in region of left brachial plexus.B, Noncontrast supine transaxial CT image obtained during cryoablation shows applicator placement. Treatment monitoring was difficult secondary to beam hardening andregional fat.C, Sagittal T1-weighted fat-saturated contrast-enhanced image in left midaxillary line before treatment shows enhancing mass (arrows) in region of brachial plexus.D, Coned-down sagittal T1-weighted fat-saturated contrast-enhanced image obtained 7 weeks after treatment at follow-up shows subclavian artery flow void (arrowhead)with area of surrounding enhancing tissue (arrows), which likely represents residual inadequately treated tumor secondary to “cold sink” effect.

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DiscussionPain related to recurrent or metastatic disease

is a cause of significant morbidity in the patientwith terminal cancer. The pain can be debilitat-ing, especially when osseous structures are in-volved. Because of the multifocal nature ofthese tumors and the overall poor health of thisgroup of patients, surgical resection is usuallynot a treatment option. In these select patients,percutaneous therapy may offer a minimally in-vasive treatment with a shorter recovery timethan more invasive methods. Percutaneous abla-tive techniques such as ethanol injection and ra-diofrequency ablation have been well-describedfor the treatment of primary and metastatic dis-ease in multiple organ systems [10–14]. Percu-taneous cryoablation has seen a more limitedrole. Treatment of prostate cancer using a percu-taneous approach has shown excellent success[4, 5]. Because the size of the cryoablation ap-plicator has decreased in recent years, percuta-neous cryoablation has been increasingly usedfor treatment of liver metastases with both CTand MRI guidance [8, 15, 16] and for treatmentof renal masses in patients with von Hippel-Lindau disease [7].

Percutaneous radiofrequency ablation ofboth intra- and extraabdominal primary andmetastatic lesions has been described usingboth CT and sonographic guidance [10–13].Radiofrequency ablation offers a minimally in-vasive local treatment option but can be limitedby local procedural pain, poor real-time visual-ization of treatment effects under CT guidance,and limited ablation volumes. Cryoablation of-fers a few specific advantages over radiofre-quency ablation, such as probable decreasedprocedure-associated pain [17] and real-timevisualization of the treatment area. Althoughthe cryoablation applicators are slightly lessexpensive than the radiofrequency ablationelectrodes, depending on tumor size, more ap-plicators are used in cryoablation offsetting thecost advantage. In addition, the start-up costsof a cryoablation system are slightly higher be-cause argon gas is required.

The ability to observe the treatment mar-gins in real-time is an essential attribute of aneffective imaging-guided treatment tech-nique. Multiple prior articles have describedthe appearance of frozen tissue on sonogra-phy, CT, and MRI [3, 9, 18–20]. The use ofsonographic guidance is limited because onlythe near edge of frozen tissue is adequately vi-sualized given that sound waves do not ade-quately penetrate frozen tissue. This problemis not a significant one intraoperatively be-cause the probe can be moved into other

planes, but it poses significant difficulty whenthe percutaneous approach is used. Con-versely, CT guidance with CT fluoroscopy of-fers clear visualization of the entire treatmentmargin in real-time, which is critical whentreating lesions near vital organs, hollow vis-cera, and the biliary tree and urinary tractwhere posttreatment strictures can occur. Themargins of the frozen tissue seen on CT do notrepresent the true margins of tumor necrosisbecause temperatures at the advancing outeredge of the ice ball are sublethal [21]. There-fore, we attempted to extend the margin offrozen tissue 1 cm beyond the tumor marginsseen on CT.

The use of multiple small (2.4-mm) tip ap-plicators allows substantial control over thesize and shape of the treatment area. This isespecially important when treating lesionswith irregular margins. We placed applicatorsat a distance of approximately 2 cm apartwithin the lesion and attempted to place appli-cators within 1 cm of the edge of visible tu-mor to achieve adequate treatment margins.The freeze zones blended smoothly betweenapplicators giving the area of frozen tissue ahomogeneous appearance on posttreatmentCT. We did have difficulty achieving ade-quate freezing of a tumor adjacent to a largevessel in the third patient. This is thought tobe secondary to what we refer to as the “coldsink” effect where the continuous inflow ofblood at body temperature does not allow ad-equate freezing of the adjacent tissue. Thiswas confirmed on follow-up imaging wherethere was residual enhancing tumor adjacentto the left subclavian artery (Fig. 2D).

Our study is limited by a small patient popu-lation and limited imaging follow-up. Furtherinvestigation with larger treatment groups, long-term follow-up, and the use of a standardizedpain-reporting scale is necessary for proof of ef-ficacy. The patients in our report had alreadyfailed conventional therapy and had very ad-vanced disease with large locally aggressive le-sions. Our preliminary results suggest thatpercutaneous imaging-guided cryoablation iswell tolerated and may play a role in the treat-ment of symptomatic local metastases.

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