Medical Plicy 7.01.133 Micrwave Tumr Ablatin Sectin 7.0 Surgery Subsectin Effective Date February 27, 2015 Original Plicy Date February 27, 2015 Next Review Date February 2016 Descriptin Micrwave ablatin (MWA) is a technique t destry tumrs and sft tissue by using micrwave energy t create thermal cagulatin and lcalized tissue necrsis. MWA is used t treat tumrs cnsidered t be inperable r nt amenable t resectin r t treat patients ineligible fr surgery due t age, presence f cmrbidities, r pr general health. MWA may be perfrmed as an pen prcedure, laparscpically, percutaneusly r thracscpically under image guidance (e.g., ultrasund, cmputed tmgraphy [CT] r magnetic resnance imaging [MRI]) with sedatin, r lcal r general anesthesia. This technique may als be referred t as micrwave cagulatin therapy. Related Plicies Crysurgical Ablatin f Primary r Metastatic Liver Tumrs Liver Transplant Radiemblizatin fr Primary and Metastatic Tumrs f the Liver Radifrequency Ablatin f Miscellaneus Slid Tumrs Excluding Liver Tumrs Radifrequency Ablatin f Primary f Metastatic Liver Tumrs Transcatheter Arterial Chememblizatin (TACE) t Treat Primary r Metastatic Liver Malignancies Plicy Lcreginal Ablatin Laser ablatin fr the treatment f patients with primary r metastatic hepatic lesins is cnsidered investigatinal. Micrwave ablatin may be cnsidered medically necessary fr the treatment f patients with hepatic lesins with any f the fllwing cnditins: Primary hepatcellular carcinma (HCC) when the all f the fllwing criteria are met: Patient is nt a candidate fr curative hepatic surgical resectins due t limited hepatic reserve and/r cmrbid cnditins and/r the lcatin (e.g., adjacent t a majr vein) r number f lesins Patient is nt a candidate fr liver transplantatin* (see exceptin belw) Presence f three r fewer hepatic lesins Each lesin measures 5 centimeters (cm) r less in diameter using current technlgy 1
Medical Plicy Absence f extrahepatic metastatic disease All tumr fci can be adequately treated (cmplete ablatin determined by preperative imaging) Primary HCC, as a bridge t transplantatin*, when all f the fllwing criteria are met: Patient is nt a candidate fr curative hepatic surgical resectins due t limited hepatic reserve and/r cmrbid cnditins and/r the lcatin (e.g., adjacent t a majr vein) r number f lesins Intent is t prevent further tumr grwth and t maintain a patient s candidacy fr liver transplant Presence f three r fewer hepatic lesins Each lesin measures 5 centimeters (cm) r less in diameter using current technlgy N evidence f extrahepatic spread and/r macrvascular invlvement (i.e., prtal r hepatic veins) Nte: Criteria fr ablative therapies as a bridge t transplantatin are generally cnsistent with the United Netwrk fr Organ Sharing (UNOS) plicy n Organ Distributin: Liver Transplant Candidates with Hepatcellular Carcinma (HCC); Sectin 3.6.4.4 (11/9/2010). Hepatic metastases frm clrectal cancer when all f the fllwing criteria are met: Patient is nt a candidate fr curative hepatic surgical resectins due t limited hepatic reserve and/r cmrbid cnditins and/r the lcatin (e.g., adjacent t a majr vein) r number f lesins Presence f fur t five r fewer hepatic lesins Each lesin measures 5 centimeters (cm) r less in diameter using current technlgy Absence f extrahepatic metastatic disease All tumr fci can be adequately treated (cmplete ablatin determined by preperative imaging) Hepatic metastases frm neurendcrine tumrs when all f the fllwing criteria are met: Patient has symptmatic disease (e.g., wheezing, flushing f the skin, abdminal cramps, diarrhea, heart disease) Systemic therapy has failed t cntrl symptms (e.g., Octretide therapy) Patient is nt a candidate fr curative hepatic surgical resectins due t limited hepatic reserve and/r cmrbid cnditins and/r the lcatin (e.g., adjacent t a majr vein) r number f lesins Absence f extrahepatic metastatic disease Each lesin measures 5 centimeters (cm) r less in diameter using current technlgy 2
Medical Plicy Micrwave ablatin fr primary HCC r hepatic metastases is cnsidered investigatinal fr treatment f any f the fllwing: Primary HCC when there are either f the fllwing: Mre than three hepatic lesins ndules When nt all sites f tumr fci can be adequately treated Primary HCC when used t dwnstage (dwnsize) HCC in patients being cnsidered fr liver transplant Hepatic metastasis frm clrectal cancer r neurendcrine tumrs nt meeting the medically necessary criteria abve Hepatic metastases frm ther types f cancer with the exceptin f clrectal r neurendcrine cancer tumrs Plicy Guidelines Dwnstaging (dwnsizing) therapy is used t reduce the tumr burden in selected patients with mre advanced HCC (withut distant metastasis) that are beynd the accepted transplant criteria. Neurendcrine Tumrs Neurendcrine tumrs (NETs) may be referred t by their anatmical lcatin (e.g., pulmnary neurendcrine tumr, gastrenterpancreatic neurendcrine tumr). Neurendcrine tumrs include the fllwing: Carcinid tumrs Islet cell tumrs (r pancreatic endcrine tumrs) Neurendcrine unknwn primary Adrenal gland tumrs Phechrmcytma/paraganglima Prly differentiated (high grade r anaplastic)/small cell Multiple endcrine neplasia, Type 1 (als knwn as MEN-1 syndrme r Wermer's syndrme) Multiple endcrine neplasia, Type 2 a r b (als knwn as phechrmcytma and amylid prducing medullary thyrid carcinma, PTC syndrme, r Sipple syndrme) Symptmatic disease frm neurendcrine tumrs may include ht, red flushing f the face, severe and debilitating diarrhea, asthma attacks, palpitatins, lw bld pressure, fatigue, dizziness, and weakness. Extreme symptms may include heart disease, brnchial cnstrictin, and bwel bstructin. Systemic therapies fr neurendcrine tumrs vary depending n the lcatin and characteristics. Therapies may include, but are nt limited t: ctretide, interfern, cyttxic chemtherapy, angigenesis inhibitrs, and epidermal grwth factr inhibitrs. 3
Medical Plicy Cding There are n CPT cdes specific t micrwave ablatin. The fllwing CPT cde wuld likely be used: 32998: Ablatin therapy fr reductin r eradicatin f 1 r mre pulmnary tumr(s) including pleura r chest wall when invlved by tumr extensin, percutaneus, radifrequency, unilateral 47370: Laparscpy, surgical, ablatin f 1 r mre liver tumr(s); radifrequency 47380: Ablatin, pen, f 1 r mre liver tumr(s); radifrequency 47382: Ablatin, 1 r mre liver tumr(s), percutaneus, radifrequency 47383: Ablatin, 1 r mre liver tumr(s), percutaneus, cryablatin (new cde 01/01/15) 50592: Ablatin, 1 r mre renal tumr(s), percutaneus, unilateral, radifrequency Nte: Accrding t a 2012 American Medical Assciatin publicatin (Clinical Examples in Radilgy, Vl. 8, Issue 3; Summer 2012), micrwave is part f the radifrequency spectrum, and simply uses a different part f the radifrequency spectrum t develp heat energy t destry abnrmal tissue. Therefre, they instruct that micrwave ablatin shuld be reprted using the CPT cdes fr radifrequency ablatin 32998 (pulmnary), 47382 (liver), and 50592 (renal). If there is n specific CPT cde fr ablatin, the unlisted CPT cde fr the anatmic area shuld be reprted such as cde 60699 fr unlisted prcedure, endcrine system (fr adrenal r thyrid ablatin). CPT cde 76940 wuld be used t describe the ultrasund guidance fr, and mnitring f, parenchymal tissue ablatin. Benefit Applicatin Benefit determinatins shuld be based in all cases n the applicable cntract language. T the extent there are any cnflicts between these guidelines and the cntract language, the cntract language will cntrl. Please refer t the member's cntract benefits in effect at the time f service t determine cverage r nncverage f these services as it applies t an individual member. Sme state r federal mandates (e.g., Federal Emplyee Prgram (FEP)) prhibit Plans frm denying Fd and Drug Administratin (FDA) - apprved technlgies as investigatinal. In these instances, plans may have t cnsider the cverage eligibility f FDA-apprved technlgies n the basis f medical necessity alne. Ratinale Backgrund Micrwave ablatin (MWA) is a technique in which the use f micrwave energy induces an ultra-high speed, 915 MHz r 2.450 MHz (2.45 GHz), alternating electric field, which causes water mlecule rtatin and the creatin f heat. This results in thermal cagulatin and lcalized tissue necrsis. In MWA, a single micrwave antenna r multiple antennas cnnected t a generatr are inserted directly int the tumr r tissue 4
Medical Plicy t be ablated; energy frm the antennas generates frictin and heat. The lcal heat cagulates the tissue adjacent t the prbe, resulting in a small, apprximately 2- t 3- cm elliptical area (5x3 cm) f tissue ablatin. In tumrs greater than 2 cm in diameter, 2 t 3 antennas may be used simultaneusly t increase the targeted area f MWA and shrten perative time. Multiple antennas may als be used simultaneusly t ablate multiple tumrs. Tissue ablatin ccurs quickly, within 1 minute after a pulse f energy, and multiple pulses may be delivered within a treatment sessin, depending n the size f the tumr. The cells killed by MWA are typically nt remved but are gradually replaced by fibrsis and scar tissue. If there is lcal recurrence, it ccurs at the edges. Treatment may be repeated as needed. MWA may be used t: (1) cntrl lcal tumr grwth and prevent recurrence; (2) palliate symptms; and (3) extend survival duratin. Cmplicatins frm MWA are usually cnsidered mild and may include pain and fever. Other ptential cmplicatins assciated with MWA include thse caused by heat damage t nrmal tissue adjacent t the tumr (e.g., intestinal damage during MWA f the kidney r liver), structural damage alng the prbe track (e.g., pneumthrax as a cnsequence f prcedures n the lung), liver enzyme elevatin, liver abscess, ascites, pleural effusin, diaphragm injury r secndary tumrs if cells seed during prbe remval. MWA shuld be avided in pregnant patients because ptential risks t the patient and/r fetus have nt been established and in patients with implanted electrnic devices such as implantable pacemakers that may be adversely affected by micrwave pwer utput. MWA is an ablative technique similar t radifrequency r crysurgical ablatin. Hwever, MWA has sme ptential hypthetical advantages ver RFA r crysurgical ablatin. In MWA, the heating prcess is active, which prduces higher temperatures than the passive heating f RFA and shuld allw fr mre cmplete thermal ablatin in a shrter perid f time. The higher temperatures reached with MWA (>100 C) can vercme the heat sink effect in which tissue cling ccurs frm nearby bld flw in large vessels, ptentially resulting in incmplete tumr ablatin. MWA des nt rely n the cnductin f electricity fr heating, and therefre, des nt have electrical current flw thrugh patients and des nt require that grunding pads be used during the prcedure, because there is n risk f skin burns. Additinally, MWA des nt prduce electric nise, which allws ultrasund guidance t ccur during the prcedure withut interference, unlike RFA. Finally, MWA can be cmpleted in less time than RFA, because multiple antennas can be used simultaneusly. MWA was first used percutaneusly in 1986 as an adjunct t liver bipsy. Since that time, MWA has been used fr ablatin f tumrs and tissue fr the treatment f many cnditins including: HCC, clrectal cancer metastatic t the liver, renal cell carcinma, renal hamartma, adrenal malignant carcinma, nn-small-cell lung cancer, intrahepatic primary chlangicarcinma, secndary splenmegaly and hypersplenism, abdminal tumrs and ther tumrs nt amenable t resectin. Wellestablished lcal r systemic treatment alternatives are available fr each f these malignancies. The hypthesized advantages f MWA fr these cancers include imprved lcal cntrl and thse cmmn t any minimally invasive prcedure (e.g., preserving nrmal rgan tissue, decreasing mrbidity, decreasing length f hspitalizatin). Hepatic Tumrs Hepatic tumrs can arise either as primary liver cancer (HCC) r by metastasis t the liver frm ther primary cancer sites. Lcal therapy fr hepatic metastasis may be indicated when there is n extrahepatic disease, which rarely ccurs fr patients with primary cancers ther than clrectal carcinma r certain neurendcrine malignancies. At 5
Medical Plicy present, surgical resectin with adequate margins r liver transplantatin cnstitutes the nly treatments available with demnstrated curative ptential. Partial liver resectin, hepatectmy, is cnsidered the criterin standard. Hwever, mst hepatic tumrs are unresectable at diagnsis, due either t their anatmic lcatin, size, number f lesins, r underlying liver reserve. Varius lcreginal therapies fr unresectable liver tumrs have been investigated including: micrwave cagulatin, RFA, crysurgical ablatin (crysurgery), laser ablatin, transhepatic artery emblizatin/chememblizatin (TACE), percutaneus ethanl injectin, and radiemblizatin (Yttrium-90 micrspheres). MWA has been investigated as a treatment fr unresectable hepatic tumrs, bth as primary treatment, palliative treatment, and as a bridge t liver transplant. In the latter setting, it is hped that MWA will reduce the incidence f tumr prgressin while awaiting transplantatin and thus maintain a patient s candidacy fr liver transplant during the wait time fr a dnr rgan. Renal Cell Carcinma Radical nephrectmy remains the principal treatment f renal cell carcinma; hwever, partial nephrectmy r nephrn-sparing surgery has been shwn t be as effective as radical nephrectmy, with cmparable lng-term recurrence-free survival rates, in a select grup f patients. Prgnsis drps precipitusly if the tumr extends utside the kidney capsule, because chemtherapy is relatively ineffective against metastatic renal cell carcinma. Alternative therapies such as MWA are f interest in patients with small renal tumrs when preservatin f renal functin is necessary (e.g., in patients with marginal renal functin, a slitary kidney, bilateral tumrs) and in patients with cmrbidities that wuld render them unfit fr surgery. Anther cnsideratin wuld be in patients at high risk f develping additinal renal cancers (as in vn Hippel-Lindau disease). Regulatry Status There are several devices cleared fr marketing by FDA thrugh the 510(k) prcess fr MWA. Cvidien s (a subsidiary f Tyc Healthcare) Evident Micrwave Ablatin System has 510(k) clearance fr sft tissue ablatin, including partial r cmplete ablatin f nnresectable liver tumrs. The fllwing devices have 510(k) clearance fr MWA f (unspecified) sft tissue: BSD Medical Crpratin s MicrThermX Micrwave Ablatin System (MTX-180); Valleylab s (a subsidiary f Cvidien) VivaWave Micrwave Ablatin System; Vivant s (acquired by Valleylab in 2005) Tri-Lp Micrwave Ablatin Prbe; MicrSurgen Micrwave Sft Tissue Ablatin Device; Micrsulis Medical s (nw part f AngiDynamics) Acculis Accu2i; and NeuWave Medical s Certus 140 These devices are cnsidered substantially equivalent t previusly FDA-apprved radifrequency and MWA devices. FDA prduct cde: NEY. This plicy des nt address MWA fr the treatment f splenmegaly r ulcers r as a surgical cagulatin tl. 6
Medical Plicy Breast A 2010 review f ablatin techniques by Zha et al fr breast cancer fund nly 0% t 8% f breast tumrs were cmpletely ablated with micrwave ablatin (MWA). 1 The authrs nted the studies identified fr the review were mstly feasibility and pilt studies cnducted in research settings. In 2012, W. Zhu et al reprted n 41 patients treated with MWA directly fllwed by mastectmy fr single breast tumrs with a mean vlume f 5.26±3.8 cm (range, 0.09-14.14 cm). 2 Cmplete tumr ablatin was fund by micrscpic evaluatin in 37 f the 41 tumrs ablated (90%; 95% cnfidence interval [CI]: 76.9% t 97.3%). Reversible thermal injuries t the skin and pectralis majr muscle ccurred in 3 patients. Hepatcellular Carcinma Primary Hepatcellular Carcinma Primary hepatcellular carcinma (HCC) cmmnly ccurs in the cntext f chrnic liver disease and cirrhsis and is ften diagnsed in its later stages. In 2006, Brwn et al reprted that althugh patients with lcalized HCC are best managed with cmplete surgical resectin, less than 20% are viable candidates because f the extent r lcatin f the lesins, cmrbid cnditins, r disseminated disease. 3 The Natinal Cmprehensive Cancer Netwrk (NCCN) Guidelines fr HCC stated, All HCC patients shuld be evaluated fr ptential curative therapies (resectin, transplantatin)." 4 Lcreginal therapies are recmmended when there is n extrahepatic disease and prgressin is limited, but cure is less likely. The NCCN des nt discriminate amng the ablative therapies in the treatment f HCC. They prpse ablatin fr hepatic lesins less than r equal t 3 centimeters (cm) in size. The NCCN additinally stated unresectable r inperable lesins greater than 5 cm shuld be cnsidered fr treatment using arterial emblic appraches r systemic therapy. The NCCN principles f lcreginal therapy are as fllws: Fr ablatin (radifrequency (RFA), cryablatin (crysurgical ablatin, CSA), percutaneus ethanl r alchl injectin (PEI r PAI), and micrwave ablatin (MWA) : All tumrs shuld be amenable t ablatin such that the tumr and margin f nrmal tissue is treated. Tumrs shuld be in a lcatin accessible fr percutaneus/laparscpic/pen appraches fr ablatin Tumrs less than 3 cm are ptimally treated with ablatin. Lesins between 3 and 5 cm may be treated using a cmbinatin f emblizatin and ablatin as lng as the tumr lcatin is favrable. Unresectable r inperable lesins greater than 5 cm shuld be cnsidered fr treatment using arterial emblic appraches r systemic therapy. Cautin shuld be exercised when ablating lesins near majr vessels, majr bile ducts, diaphragm, and ther intra-abdminal rgans. The Natinal Cancer Institute's (NCI) Physician Data Query (PDQ) regarding adult primary liver cancer treatment listed PEI, CSA, RFA, and chememblizatin as standard treatment alternatives fr patients with unresectable primary HCC tumrs under 5 cm in diameter. 5 Identified cntraindicatins t emblizatin (with r withut chemtherapy) include prtal hypertensin, prtal vein thrmbsis, and clinical jaundice. New medical appraches are being researched in clinical trials including, but nt limited t, targeted therapy after chememblizatin r cmbined with chemtherapy, and cmbinatin 7
Medical Plicy therapy with surgery, chemtherapy, and radiatin therapy. The literature search identified many publicatins n studies f MWA fr hepatcellular carcinma (HCC), primarily small case series and retrspective reviews cnducted in China and Japan. Only 2 studies were indexed in the PubMed database as randmized cntrlled trials (RCTs). 6,7 N RCTs cmparing the use f MWA fr HCC with the criterin standard f surgical resectin were identified. The fllwing summarizes systematic reviews 8,9 and select studies reprting n 25 r mre patients. All f the studies demnstrated that the technique f MWA prvided gd tumr ablatin (87%-100% ablatin f targeted tumrs) with lw prcedural cmplicatin rates. Assciated mrbidity and mrtality, as well as verall survival (OS) and disease-free survival rates with MWA are similar t radifrequency ablatin (RFA), which wuld be an apprpriate cmparatr in patients with tumrs nt amenable t surgical resectin. Hwever, nly 1 RCT cmparing MWA directly with RFA was identified. 10 In 2009, Ong et al cnducted a systematic review f studies n MWA fr primary and secndary liver tumrs. 8 Based n the results frm 25 clinical studies reprting utcmes n MWA, the authrs cncluded MWA is an effective and safe technique fr liver tumr ablatin with lw cmplicatin rates and survival rates cmparable with hepatic resectin. Hwever, rates f lcal recurrence after MWA were nted t be higher than hepatic resectin. In mst studies, HCC recurrence rates were apprximately 10% but were als nted t be as high as 50%, which the authrs indicated can be addressed with further ablatin. Survival rates in the studies n MWA fr HCC were as high as 92% at 3 years and 72% at 5 years, which was nted t be cmparable with RFA and percutaneus ethanl injectins. Pain and fever were the mst frequently reprted cmplicatins, but cmplicatins increased when there were mre tumrs, larger tumrs, and mre micrwave antennas used. Ong et al cncluded MWA is a prmising treatment ptin fr the treatment f liver tumrs but shuld be reserved fr patients nt amenable t hepatic resectin. The authrs als nted further RCTs are warranted t cmpare MWA with ther ablatin prcedures. Bertt et al cnducted a systematic review in 2011 f ablatin techniques fr primary and secndary liver tumrs. 9 This review included 2 studies using MWA ttaling 1185 patients. 13,14 The pled mrtality rate fr MWA was 0.23% (95% CI: 0.0% t 0.58%). Majr cmplicatin rates were 4.6% fr MWA (calculated by using a randm effects mdel, because there was significant hetergeneity). The authrs cncluded percutaneus ablatin techniques, including MWA, are safe and have acceptable cmplicatin rates fr the treatment f liver tumrs. In 2002, Shibata et al reprted n 72 cnsecutive patients with 94 small HCC ndules randmized by sealed envelpes t receive either percutaneus MWA r RFA perfrmed by a single surgen. 6 N significant differences were identified between the 2 treatment grup characteristics, eg, sex, age, ndule size, Child-Pugh cirrhsis class and number f ndules. In the RFA grup, cmplete therapeutic effect was seen in 46 (96%) f 48 ndules (mean size, 2.3 cm; range, 1.0-3.7) versus 41 (89%) f 46 ndules (mean size, 2.2 cm; range, 0.9-3.4) treated with percutaneus MWA (p=0.26). Treatment utcmes were nt significantly different between the percutaneus MWA and RFA grups in the rates f untreated disease during a fllw-up range f 6 t 27 mnths (8/46 ndules vs 4/48 ndules, respectively), and majr cmplicatin rates (4 vs 1, respectively). Majr cmplicatins included 1 case f segmental hepatic infarctin in the RFA grup. In the MWA grup, majr cmplicatins included 1 case f each f the fllwing: liver abscess, chlangitis with intrahepatic bile duct dilatatin, subcutaneus abscess with skin burn and subcapsular hematma. Life-threatening cmplicatins were nt experienced. The number f treatment sessins required per ndule in the RFA grup was significantly lwer than in the percutaneus MWA grup (1.1 vs 2.4; p<0.001). Hwever, treatment 8
Medical Plicy time per sessin was significantly shrter in the MWA grup (33±11 minutes) than the RFA grup (53±16 minutes). Taniai et al, in 2006, reprted n 30 patients with multiple HCC tumrs wh underwent reductin hepatectmy with pstperative transcatheter arterial emblizatin. 7 Befre surgery, patients were randmly assigned t receive n intraperative adjuvant therapy (n=15) r intraperative adjuvant therapy with either MWA (n=10) r RFA (n=5) f satellite lesins. N significant differences in characteristics were identified between the 2 treatment grups f n intraperative adjuvant therapy versus intraperative adjuvant therapy, eg, sex, age, ndule size (maximum tumr size, 42.7±23.5 mm vs 37.8±16 mm, respectively), Child-Pugh cirrhsis class and number f ndules. Cumulative survival rates at 3 and 5 years were nt significantly different in the grup that did nt receive intraperative adjuvant therapy (35.0% and 0%, respectively) versus the intraperative adjuvant therapy grup (35.7% and 7.7%, respectively). A-fetprtein, number f tumrs, maximum tumr size, and clinical stage, but nt intraperative adjuvant therapy, was identified as independent prgnstic survival factrs. In April 2011, Sim et al retrspectively cmpared laparscpic MWA (13 patients with 15 tumrs) with RFA (22 patients with 27 tumrs) perfrmed by a single surgen fr the treatment f HCC. 12 N significant differences were identified between the 2 treatment grup characteristics except fr sex (54% vs 86% male, respectively). Average tumr size was 2.31 cm in the MWA grup versus 2.53 cm in the RFA grup. The authrs reprted average tumr ablatin vlumes were nt significantly different at 28.99 cm fr MWA and 23.43 cm fr RFA. In the MWA grup, at a mean fllw-up f 7 mnths, disease-free survival was 54%, with 2 patients having received liver transplants, 31% having disease prgressin and 15% deceased. The RFA grup was fllwed fr a lnger perid f time at a mean f 19 mnths. This grup experienced 50% survival withut evidence f disease, with 4 patients having received liver transplants, 9% having disease prgressin, 36% deceased, and 5% lst t fllw-up. Operative times were shrter in the MWA grup (112±40 vs 149±35 minutes). In 2013, Ding et al als reprted n a retrspective cmparisn f 113 patients treated with MWA fr 131 HCC tumrs and 85 patients treated with RFA fr 98 HCC tumrs. 13 Rates f cmplete ablatin, lcal recurrence, disease-free and cumulative survival (at 1, 2, 3, and 4 years), and majr cmplicatins were nt significantly different between grups. In anther 2013 study by Ding et al, cmplicatins were retrspectively cmpared between 556 patients treated with MWA fr 1090 tumrs (491 HCC, 18 chlangicarcinma, 47 liver metastases) and 323 patients treated with RFA fr 562 liver tumrs (279 HCC, 6 chlangicarcinma, 38 liver metastases). 14 Rates f death (2/556 MWA, 1/323 RFA patients), majr cmplicatins and minr cmplicatins did nt differ significantly between MWA and RFA grups. In 2011, Zhu et al prspectively evaluated percutaneus MWA fr HCC in 215 patients with tumrs f 60 mm r less (median size, 29 mm) in a single center, Phase 2 study. 15 The authrs reprted technical effectiveness in all patients. OS rates at 1, 2, 3, 4, and 5 years were 94%, 82.9%, 66%, 54.1%, and 44.4%, respectively, and median survival time was 40 mnths (range, 4-106 mnths). Cmplicatins related t the prcedure included 3 cases f pleural effusin and 1 case f bile duct injury. In anther prspective study by Zhu et al in 2009, percutaneus MWA was perfrmed n 124 patients with 144 HCC lesins and 28 patients with 35 lesins f hepatic metastases. 16 Included in this ttal f 152 patients were 59 patients with 61 lesins (mean size, 27 mm) lcated less than 5 mm frm the gastrintestinal tract and 93 patients with 126 lesins (mean size 24 mm) lcated mre than 5 mm frm the gastrintestinal tract. Fr lesins less than 5 mm frm the gastrintestinal tract, the temperatures f the margins were mnitred clsely during ablatin and t prevent thermal injury, ethanl injectins were placed int marginal tumr tissue in 33 lesins that were prtruding r in cntact with the gastrintestinal tract. 9
Medical Plicy N prcedural cmplicatins were nted; hwever, tumr seeding ccurred in 3 patients. Cmplete ablatin was achieved in 47 f 53 lesins (88.7%) in the grup with tumrs near the gastrintestinal tract and in 116 f the ther 126 lesins (92.1%), as cnfirmed by imaging during the fllw-up perid ranging frm 3 t 32 mnths. Lcal tumr prgressin ccurred in 16 tumrs during 1- t 9-mnth fllw-up. Separate treatment utcmes fr hepatcellular tumrs and hepatic metastasis were nt prvided. Lu et al, in 2005, reprted n a retrspective cmparisn f 102 patients with HCC treated with either percutaneus MWA (49 patients with 98 ndules; mean size, 2.5 cm) r RFA (53 patients with 72 ndules; mean size, 2.6 cm). 10 Patient fllw-up was 25.1 mnths in the MWA grup and 24.8 mnths in the RFA grup. Cmplete ablatin was nt significantly different in the treatment grups and was achieved in 93 f 98 tumrs (94.9%) in the MWA grup and in 67 f 72 tumrs (93.1%) in the RFA grup. Hwever, cmplete ablatin rates increased in tumrs less than r up t 3 cm in size t 98.6% (73/74) in the MWA grup and 98% (50/51) in the RFA grup. In tumrs greater than 3 cm, cmplete ablatin rates decreased t 83.3% (20/24) in the MWA grup and 81% (17/21) in the RFA grup. There were als n significant differences fund in the MWA grup versus the RFA grup in rates f lcal tumr recurrence (11.8% vs 20.9%, respectively), majr cmplicatins (8.2% vs 5.7%, respectively) r disease-free survival at 1, 2, and 3 years (45.9%, 26.9%, and 26.9% vs 37.2%, 20.7%, and 15.5%, respectively). In 2012, Takami et al reprted n 719 patients treated with intraperative MWA fr HCC (mean tumr size, 26.9 mm) at a single institutin. 17 The OS rates were 97.7% at 1 year, 62.1% at 5 years, and 34.1% at 10 years. OS rates fr 390 patients with 3 r fewer tumrs measuring 3 cm r less were 97.9% at 1 year, 70.0% at 5 years, and 43.0% at 10 years. When MWA results were cmpared with 34 patients treated at the same institutin with hepatic resectin, OS, disease-free survival, and lcal recurrence rates were nt significantly different. In 2009, Liang et al reprted n a retrspective review f cmplicatins experienced with percutaneus MWA fr the treatment f 1928 malignant liver tumrs in 1136 patients at a single institutin. 11 Each patient received an average f 1.8 treatment sessins fr a ttal f 3697 treatment sessins. Thirty patients (2.6%) experienced majr cmplicatins, which included 5 cases f liver abscess and empyema, 2 bile duct injuries, 2 cln perfratins, 5 tumr seedings, 12 pleural effusins requiring thracentesis, 1 hemrrhage requiring arterial emblizatin, and 3 skin burns requiring resectin fr a ttal f 30 (2.6%) patient cmplicatins. Tw deaths ccurred within 30 days after MWA in patients with Child class B uncmpensated cirrhsis. One patient (age 78) had multi-rgan failure and died 14 days after treatment and anther patient (age 83) had respiratry and cardiac failure and died 14 days after treatment. Minr cmplicatins included fever (83.4%), pain (80.1%), asymptmatic pleural effusin (10.4%), thickening f the gallbladder wall (2.8%), and arteriprtal shunt (0.3%), small stricture f the bile duct (0.4%), and skin burn requiring n treatment (1.6%). A significantly higher rate f majr cmplicatins and mre ablatin sessins were experienced when a nncled-shaft antenna was used during the perid f 1994 t 2005 (n=583) than with newer technlgy; cled-shaft antennas were used beginning in 2005 (n=583). In a reprt n needle-track seeding frm this same institutin, Yu et al fllwed 1462 patients treated with percutaneus MWA fr 2530 liver tumrs ver a 14-year perid. 18 Twelve seeding ndules with a mean size f 2.3±0.7 cm (range, 1.3-3.9 cm) were fund in 11 patients within 6 t 37 mnths (median 10 mnths) after receiving MWA. 10
Medical Plicy Hepatic Metastasis Frm Primary Cancers Frm Other Sites The literature searches identified many small studies n MWA fr hepatic metastases, 1 RCT, and several systematic reviews. 8,9,19-21 A 2014 Health Technlgy Assessment 21 and a 2013 Cchrane review 20 als identified nly 1 RCT n ablatin fr liver metastasis, Shibata et al, 22 (described next). The reviewers fund insufficient evidence t determine any benefits f MWA fr liver metastasis ver surgical resectin. In the Ong systematic review (previusly described) lcal recurrence rates fr liver metastases after treatment with MWA averaged apprximately 15% but varied between 0% and 50% in the 7 studies reviewed that addressed liver metastases. As nted earlier, Ong et al cncluded MWA is a prmising treatment ptin fr the treatment f liver tumrs but shuld be reserved fr patients nt amenable t hepatic resectin. Bertt et al cnducted a systematic review, als described earlier. 9 In 2011, Pathak et al cnducted a systematic review f ablatin techniques fr clrectal liver metastases, which included 13 studies n MWA ttaling 406 patients with a minimum f 1-year fllw-up. 19 Mean survival rates were 73%, 30%, and 16% and ranged frm 40% t 91.4%, 0% t 57%, and 14% t 32% at 1-, 3-, and 5-year fllw-up, all respectively. Minr and majr cmplicatin rates were cnsidered acceptable and ranged frm 6.7% t 90.5% and 0% t 19%, respectively. Lcal recurrence rates ranged frm 2% t 14%. The authrs acknwledged limitatins in the available studies but cncluded that survival rates fr MWA are mre favrable than fr palliative chemtherapy alne. Only 1 RCT cmparing the use f MWA fr hepatic metastases t the criterin standard f surgical resectin was identified. In 2000, Shibata et al reprted n a trial f 30 patients with hepatic metastases frm clrectal cancer randmly assigned withut stratificatin t treatment with either MWA after lapartmy (n=14) r hepatectmy (n=16). 22 The study began with 40 patients, but 10 patients were excluded because the researchers discvered intraperatively that these patients did nt meet study criteria due t having extensive metastasis r 10 r mre tumrs. The treatment grups f MWA versus hepatectmy were nt significantly different in age (mean age, 61 years in bth grups) number f tumrs (mean 4.1 vs 3.0, respectively) r tumr size (mean 27 mm vs 34 mm, respectively). The authrs reprted n significant differences in survival rates fllwing MWA r hepatectmy (27 mnths vs 25 mnths, respectively) and mean disease-free survival (11.3 vs 13.3 mnths, respectively). Hwever, intraperative bld lss was significantly lwer and n bld transfusins were required in the MWA grup, whereas 6 patients in the hepatectmy grup required bld transfusins. Cmplicatins in the micrwave grup cnsisted f 1 hepatic abscess and 1 bile duct fistula. In the hepatectmy grup, cmplicatins were 1 intestinal bstructin, 1 bile duct fistula, and wund infectin. In 2011, Lrentzen et al reprted n a retrspective review f percutaneus r pen MWA in 39 patients with 125 liver metastases frm the primary sites f clrectal cancer (n=31), breast cancer (n=6), carcinid tumr (n=1), and gastrintestinal strmal tumr (n=1). 23 Cmplete ablatin was achieved in 100% f tumrs (median size, 1.5 cm) with 1 treatment sessin in 34 patients, 2 sessins fr 4 patients, and 3 sessins fr 1 patient. One case f liver abscess, which reslved after percutaneus drainage, was the nly majr cmplicatin reprted. Fur minr cmplicatins included 1 incidence f ascites and 3 cmplaints f puncture site pain. At median fllw-up f 11 mnths, lcal tumr prgressin was seen in 12 f 125 tumrs (9.6%) in 10 f the 39 patients (26%). In a prspective, single institutin Phase 2 study in 2010, Martin et al reprted n 100 patients treated with 270 pen r laparscpic MWAs fr HCC (n=17) and liver metastases frm the primary sites f clrectal (n=50), carcinid (n=11), and ther cancers (n=22 and included chlangicarcinma, metastatic breast, renal cell 11
Medical Plicy carcinma, bladder, carcinid, melanma, and sarcma). 24 Median tumr size was 3.0 cm. Thirty-eight patients were treated with MWA alne, 53 patients had MWA with cncmitant hepatic resectin while anther 9 patients had MWA cncmitant with ther rgan resectin. Only 2 patients had incmplete ablatins after the prcedure. N bleeding cmplicatins were experienced, but 2 cases f hepatic abscess and 2 cases f hepatic insufficiency ccurred. At median fllw-up f 36 mnths, 5 patients were fund t have incmplete ablatins and nly 2 patients (2%) had lcal tumr recurrence, while 37 patients (37%) develped recurrence at ther nnablated sites. In 2013, Liu et al reprted n 35 patients treated with MWA fr 62 tumrs and 54 patients treated with RFA fr 70 tumrs frm liver metastases. 25 Ablatin was cmplete in 88.6% (117/132) f tumrs and was nt significantly different between tumr types: 86.2% fr metastatic clrectal cancer (56/65) and 91% fr ther metastatic disease 61/67). Nr was there a significant difference between MWA and RFA in the cmplete ablatin rate. Tumrs 3.0 cm r less were cmpletely ablated significantly mre ften than tumrs greater than 3.0 cm (93.5 vs 66.7%, p=0.001). Lung Several studies have reprted experience using MWA fr lung tumrs. 26-28 In 2012, Lu et al reprted n a retrspective review f 69 patients treated with MWA fr inperable lung cancer r metastatic pulmnary metastases. 29 OS rates fr patients with pulmnary metastases at 1 year, 2 years, and 3 years were 47.6%, 23.8%, and 14.3%, respectively. The recurrence-free survival rates fr patients with nn-small cell lung cancer at 1 year, 2 years, and 3 years were 72.9%, 50.0%, and 27.1%, respectively. OS rates were 66.7% at 1 year, 44.9% at 2 years, and 24.6% at 3 years. N deaths ccurred within 30 days f the prcedure; hwever, pneumthrax ccurred in 24.64%. In 2012, Belfire et al reprted n a retrspective review f 56 patients treated with MWA fr inperable lung cancer r metastatic pulmnary metastases. 31 Disease-specific survival rates were 69% at 1 year, 54% at 2 years, and 49% at 3 years. Pneumthrax was reprted in 18 patients (32.12%). In 2011, Vgl et al reprted n a prspective study f 80 patients treated with MWA fr inperable pulmnary metastases. 31 Survival rates were 91.3% at 1 year and 75% at 2 years. N deaths ccurred within 60 days f the prcedure; hwever, pneumthrax ccurred in 11 f 130 MWA sessins (8.5%), and pulmnary hemrrhage ccurred in 8 f 130 sessins (6.2%). Primary Renal Tumrs In a 2014 systematic review and meta-analysis, Katsans et al cmpared thermal ablatin (MWA and RFA) with surgical nephrectmy fr small renal tumrs (mean size 2.5 cm). 32 Included in the analysis were 1 randmized study n MWA 33 (described next) and 5 chrt studies n RFA with a ttal f 587 patients. In the ablatin grup, the cmplicatin rates and renal functin decline were significantly lwer than in the nephrectmy grup (p=0.04 and p=0.03, respectively). The lcal recurrence rate was 3.6% in bth grups (risk rati=0.92, 95% CI: 0.4 t 2.14, p=0.79) and disease-free survival up t 5 years was nt significantly different between grups (hazard rati=1.04, 95% CI: 0.48 t 2.24, p=0.92). Martin et al reprted n a meta-analysis f MWA versus cryablatin fr small renal tumrs in 2013. 34 Included in the analysis were 7 MWA studies (n=164) and 44 cryablatin studies (n=2989). The studies were prspective r retrspective, nnrandmized, nncmparative studies. The mean fllw-up duratin was shrter fr MWA than cryablatin (17.86 mnths vs 30.22 mnths, p=0.07). While the mean tumr size was significantly larger in the MWA studies than the cryablatin studies (2.58 cm vs 3.13 cm, respectively, p=0.04), lcal tumr prgressin (4.07% vs 2.53%, respectively; 12
Medical Plicy p=0.46), and prgressin t metastatic disease (0.8% vs 0%, respectively; p=0.12) were nt significantly different. In 2012, Guan et al reprted n a prspective randmized study t cmpare the use f MWA with partial nephrectmy (the criterin standard f nephrn-sparing surgical resectin) fr slitary renal tumrs less than 4 cm. 33 Frty-eight patients received MWA and 54 had partial nephrectmy. Patients in the MWA grup had significantly fewer pstperative cmplicatins than the partial nephrectmy grup (6 [23.5%] vs 18 [33.3%]; p=0.019). MWA patients als had significantly less pstperative renal functin declines (p<0.009) and estimated periperative bld lss (p<0.001) than partial nephrectmy patients. At last fllw-up, estimated glmerular filtratin rate declines in bth grups were similar (p=1.000). Disease-specific deaths did nt ccur, and verall lcal recurrence-free survival by Kaplan-Meier estimates at 3 years were 91.3% fr MWA and 96.0% fr partial nephrectmy (p= 0.541). Lnger fllw-up is needed. Several small case studies n renal tumrs have been reprted. In 2012, Yu et al reprted n a retrspective review f 46 patients treated with MWA fr renal cell carcinma. 35 Cmplete ablatin ccurred in 98% f tumrs (48 f 49), which had a mean tumr size f 3.0±1.5 cm. At a median fllw-up f 20.1 mnths, all 46 patients were metastasis-free. OS rates were 100% at 1 and 2 years and 97.8% at 3 years. In 2011, Mut et al reprted cmplete tumr cagulatin necrsis in 10 patients treated with laparscpic MWA fr clear cell renal carcinma with a median tumr size f 2.75 cm. 36 Depending n tumr size, the micrwave antennas were used 1 t 3 times fr a mean applicatin time f 14.1 minutes. N cmplicatins were reprted during r after the prcedure. Bai et al in 2010, reprted cmplete laparscpic MWA in 17 f 18 clear cell renal carcinma tumrs with a mean tumr size f 2.8 cm. 37 In this study, evidence f disease prgressin was nt fund in any f the patients fllwed up fr a median f 20 mnths, including the patient with an incmplete ablatin wh was fllwed fr 31 mnths. Cmplicatins reprted were mild (18.2%), and renal functin did nt significantly deterirate. Hwever, in a 2011 study f 10 patients with slid-enhancing renal tumrs (median size f 3.65 cm), treated with laparscpic (n=7) r percutaneus (n=3) MWA, Castle et al reprted tumr recurrence was seen in 3 f 8 tumrs n mean fllw-up time f 17.9 mnths. 38 Because tumr size was larger in this study, mean ablatin time was 21 minutes. Additinally, 20% f patients experienced intraperative cmplicatins while 40% experienced pstperative cmplicatins including, perinephric hematma, splenic capsular tear, pleuritic chest pain, skin burn, fever, hematuria, genitfemral neuralgia, and urinma. In anther study, Guan et al reprted n the safety f retrperitnescpic MWA fr renal hamartma in 2010. 39 In this case series reprt, 15 f 16 patients had cmplete tumr ablatin. Disease recurrence was nt fund in all 16 patients at a median fllwup f 16 mnths. Other Tumrs r Cnditins N RCTs n the use f MWA fr ther tumrs r cnditins were identified. Case studies and retrspective reviews n MWA fr adrenal carcinma, 40 metastatic bne tumrs, 41 intrahepatic primary chlangicarcinma, 42 benign thyrid tumrs, 43 and ther nnnclgic cnditins (ie, bleeding peptic ulcers, esphageal varices, secndary hypersplenism) were identified. A systematic review f ablatin therapies, including MWA, fr lcally advanced pancreatic cancer was published in 2014. 44 The reviewers fund limited available evidence n MWA fr pancreatic cancer. Therefre, withut randmized studies, n cnclusins culd be drawn n thermal ablatin methds fr pancreatic cancer. 13
Medical Plicy The Sciety f Interventinal Radilgy published a psitin statement in 2009 n percutaneus RFA fr the treatment f liver tumrs. 45 It is the psitin f the sciety that percutaneus RF ablatin f hepatic tumrs is a safe and effective treatment fr selected patients with HCC and clrectal carcinma metastases and the current literature was insufficient t supprt any recmmendatins supprting r refuting the use f RFA in ther diseases. The published evidence fr demnstrating imprved health utcmes with ablative therapies f ther hepatic metastatic tumrs is lacking. Cmparative trials are needed fr these malignancies that may have assciated systemic disease. While lcreginal ablative therapy is included in the NCCN Guidelines fr CRC and neurendcrine tumrs, ablative therapy is nt recmmended fr all ther metastatic tumrs t the liver. Lcreginal Ablative Therapies There is research available fr each f the ablative therapies. Hwever, many f the studies cmbine multiple ablative prcedures r utilize ablative techniques as an adjunct t surgical resectin r chemtherapy. Studies als include patients with a brad range f tumr size and etilgy. As a result, it is smetimes difficult t draw specific cnclusins regarding the efficacy f an ablative technique. Careful selectin f candidates fr each treatment ptin and expert applicatin f these treatments are required t achieve best utcmes. Laser Ablatin Laser ablatin (LA), als knwn as laser cagulatin therapy, laser interstitial tumr therapy (LITT), and laser interstitial phtcagulatin, refers t thermal tissue destructin by cnversin f absrbed light (usually infrared) int heat. 46,47 The infrared energy penetrates tissue directly fr a distance f 12 t 15 millimeters (mm) and temperatures abve 60 degrees centigrade cause rapid cagulative necrsis and instant cell death. The mst widely used device fr LA techniques is the Nd: YAG (nedymium: yttrium- aluminium-garnet) laser (Flexilase; Living Technlgy, Glasgw, Sctland) with a wavelength f 1064 nanmeters (nm). Additinally, mre cmpact dide lasers with shrter wavelengths (800 nm t 980 nm) have been utilized. 47 A range f imaging mdalities have been used t guide percutaneus LA techniques including ultrasund-guided needle placement, and magnetic resnance (MR) with cntrast. Hwever, the use f this technique is limited by the amunt f lcal experience and resurce/machine availability. Laser ablatin has been primarily studied in the treatment f brain, spine, and prstate tumrs, but has been cleared by the U.S. Fd and Drug Administratin (FDA) fr any sft tissue tumr (FDA, 2010). Percutaneus LA has received increasing attentin fr the treatment f a variety f primary and secndary malignant tumrs, including hepatic tumrs. Hwever, f all the ablatin techniques fr hepatic tumrs, LA has the least amunt f published literature. 48 Laser ablatin is mainly applied in Eurpe and the majrity f data reprted n laser ablative techniques came frm Italy, Germany, and the United Kingdm (Gugh-Palmer & Gedryc, 2008). 47 The majrity f lng-term survival data was reprted n hepatic metastases and varied in the literature; virtually n data has been published fr HCC LA. 49 Five-year survival rates f 26% and median survival rates f 27 t 39 mnths have been reprted. 50,51 Pacella and clleagues reprted n a series f 148 patients (144 bipsy prven HCC) treated with 239 laser ablative sessins. 52 The authrs quted lng-term survival rates f 89% at ne year, 52% at three years, and 27% at five years and an verall cmplete lesin ablatin rate f 82%. Puls et al reprted n 87 cnsecutive patients with 180 liver metastases frm CRC wh underwent laser ablatin with MR thermmetry in 170 14
Medical Plicy sessins. 53 Median survival time was 54 mnths and survival rates were 95.7% at ne year, 86.2% at tw years, 72.4% at three years, 50.1% at fur years, and 33.4% at five years. Althugh, these results appeared encuraging, direct cmparisn with ther ablative therapies (e.g., RFA) in prspective clinical trials are needed t shw definitively which mdality is superir. Selectin criteria in these studies varied n the technique used and the facilities available but were in general, similar t ther lcally ablative techniques such as RFA and MWA. Many f the studies were perfrmed n multiple tumr types, making it difficult t evaluate the efficacy f laser ablatin. The range f imaging mdalities used at fllw-up cmbined with a variety f definitins f treatment success, made cmparisn f the data difficult. 47 The NCCN guidelines fr HCC d nt include r discuss LA as a technique f lcreginal ablatin. 54 While laser ablatin appears safe, evaluatin f its effectiveness is limited by lack f gd cmparative trials and hampered by cnstantly changing technlgies. The clinical efficacy f laser ablatin has nt been established at this time. 47,48 Further data frm randmized studies evaluating the impact f LA n survival, quality f life, and csteffectiveness fr bth primary and secndary liver tumrs is required. Unresectable Hepatcellular Carcinma Tumrs in the Transplant Setting As nted earlier, liver transplantatin is the nly curative alternative fr unresectable HCC. Lcreginal therapies (e.g., ablatin, TACE) have been explred in varius settings including as a technique t prevent tumr prgressin in patients n the liver transplant waiting list, dwnstaging tumrs such that the patient will be cnsidered a better candidate fr liver transplantatin, and decreasing the incidence f pst-transplant recurrence in patients with larger (T3) tumrs. All f these indicatins are in part related t the United Netwrk fr Organ Sharing (UNOS) liver allcatin plicy, which priritizes patients fr receiving dnr livers. 55 The UNOS plicy recgnized pretransplant lcreginal therapies including chememblizatin f lesin, radifrequency, cry, r chemical ablatin f the lesin, as a cmpnent f patient management during the waiting perid. In 2002, UNOS intrduced a new liver allcatin system, mdel fr endstage liver disease (referred t as MELD) fr adult patients awaiting liver transplant. 56 The MELD scre is a cntinuus disease severity scale incrprating bilirubin, prthrmbin time (i.e., internatinal nrmalized rati [INR]), and creatinine int an equatin, prducing a number that ranges frm 6 (less ill) t 40 (gravely ill). Aside frm thse in fulminant liver failure, dnr livers are priritized t thse with the highest MELD number. This scale accurately predicts the risk f dying frm liver disease except fr thse with HCC, wh ften have lw MELD scres since bilirubin, INR, and creatinine levels are near nrmal. Therefre, patients with HCC are assigned additinal allcatin pints accrding t the size and number (T stage) f tumr ndules as fllws: T1: One ndule, 1.9 cm r smaller T2: One ndule between 2.0 t 5.0 cm, r tw r three ndules each smaller than 3.0 cm T3: One ndule larger than 5.0 cm, r tw r three ndules with at least ne larger than 3.0 cm In cnsidering hw t allcate the scarce dnr rgans, UNOS sught t balance risk f death n the waiting list against risk f recurrence after transplant. Patients with T1 lesins were cnsidered at lw risk f death n the waiting list, while thse with T3 lesins are at 15
Medical Plicy high risk f pst-transplant recurrence, and are generally nt cnsidered transplant candidates. Patients with T2 tumrs have an increased risk f dying while n the waiting list cmpared t thse with T1 lesins and an acceptable risk f pst-transplant tumr recurrence. Therefre, UNOS criteria priritize T2 HCC by allcating additinal pint s equivalent t a MELD scre predicting a 15% prbability f death within three mnths. This definitin f T2 lesins is ften referred t as the Milan criteria, in reference t a key study reprted by Mazzaferr et al that examined the recurrence rate f HCC accrding t the size f the initial tumr. 57 Nte that liver transplantatin fr thse with T3 HCC is nt prhibited, but these patients d nt receive any pririty n the waiting list. All patients with HCC awaiting transplantatin are reassessed at three-mnth intervals. Thse whse tumrs have prgressed and are n lnger T2 tumrs will lse the additinal allcatin pints. Therefre, the UNOS allcatin system prvides strng incentives t use lcreginal therapies t dwnsize tumrs t T2 status and t prevent prgressin while n the waiting list. Prmfet et al reprt f a natinal cnference n liver allcatin in patients with HCC in the U.S. addressed the need t better characterize the lng-term utcmes f liver transplantatin fr patients with HCC and t assess whether it is justified t cntinue the plicy f assigning increased pririty fr candidates with early stage HCC n the transplant waiting list in the U.S.. 58 At the cmpletin f the meeting, there was a general cnsensus fr the develpment f a calculated cntinuus HCC pririty scre fr ranking HCC candidates n the list that wuld incrprate the calculated MELD scre, alphafetprtein, tumr size, and rate f tumr grwth and that nly candidates with at least stage T2 tumrs wuld receive additinal HCC pririty pints. Lcreginal Therapies as a Bridge t Transplant Several studies have reprted drput rates f wait-listed patients treated with lcreginal therapy. Hwever, lacking cntrlled data, it is difficult t assess cntributins f lcreginal therapy t time n the waiting list. In additin, in 2002, as discussed abve, UNOS revised its liver allcatin plicy, such that wait times fr patients with HCC meeting the Milan criteria have nw declined. 56 The majrity f the literature has fcused either n TACE r a variety f lcreginal therapies. Given these limitatins the fllwing case series have been reprted: Graziadei et al reprted n 48 patients with HCC awaiting transplantatin; all underwent TACE every six t eight weeks until a cmplete respnse r a dnr rgan became available. 59 N patients were remved frm the list due t tumr prgressin and mean waiting time was 178 (+/- 105) days. Maddala et al studied the drput rates f 54 patients receiving TACE while awaiting transplantatin. 60 During a median waiting time f 211 days (range: 28 t 1,099 days), the drput rate was 15%. Obed et al reprted n 20 patients with nn-prgressin f lesins after TACE wh had liver transplantatin; median survival in this grup was 92.3 mnths. 61 Fisher et al reprted n 33 patients wh received multimdality ablatin therapy, cnsisting primarily f RFA r TACE. 62 Five patients (12%) were remved frm the waiting list after waits f five t 14 mnths. In this prtcl, patients with tumrs larger than 5 cm were nt cnsidered transplant candidates until the tumr was cmpletely ablated using TACE, RFA, r anther technique. Yamashiki et al reprted n 288 patients given varius ablative therapies; the drput rate due t tumr prgressin at ne and three years was 6.25 and 23%, respectively. 63 Tumrs larger than 3 cm affected the drput rate due t tumr prgressin. Mazzaferr et al reprted n 50 patients with HCC wh underwent RFA while awaiting transplantatin; n patient had t be remved frm the waiting list due t tumr prgressin ver a mean wait time f 9.5 mnths. 64 The median tumr size was 3 16