preop mri

preop mri

RISONANZA MAGNETICA:LO STANDARD PER TUTTTE?Francesco SardanelliUniversità degli Studi di Milano, IRCCS Policlinico San Donato, Milano, ItalyEuro AIM – European Network for Assessment of Imaging in Medicine,

ArticlesArticles in PubMed 1960-2009100%VAB80%FNACCB60%US40%Mammography20%0%1960-69 1970-79 1980-89 1990-99 2000-09Mammography (n=22524) 1952, Gros & SingristUS (n=7261)1954, Howry et alFNAC (n=3961)1971, TommesenCore-biopsy (n=2130)CE-MRI (n=4608)VAB (n=394)1982, Foster1986, Heywang1997, Burbank

10 Breast MRI IndicationsEvaluated by the EUSOMA WG1. Staging (Preoperative MRI)2. Screening high-risk women3. Evaluation of response to NAC4. Augmentation or reconstruction5. Occult primary breast cancer6. Local recurrence7. Nipple discharge8. Equivocal findings at mammo/US9. Inflammatory breast cancer10. Male breast

Background #1The meta-analysis of 6 RCTs confirmsthe preference for BCT, but:4 of 6 RCTs show that mastectomysignificantly reduces the risk oflocoregional recurrence whencompared with BCT, with a significantbenefit for mastectomy (OR = 1.561)Jatoi et al, Am J Clin Oncol 2005

Background #2Breast conserving surgery has always been aimedat completely excising the tumoral tissue and atobtaining clear margins.But…In a population-based screening program, of 1,648 women who hadconserving treatment, surgical margins were:>1 mm = clear 70%1 mm = close 16%Involved 14%Re-excision in 17%, of whom 33% had residual disease identifiedKurniawan et al, Ann Surg Oncol 2008

PREOP MRIMany studies 1-11 have demonstrated the possibility:• To precisely evaluate the index lesion extent• To detect multifocal and multicentric cancers• To detect synchronous contralateral cancers• To change the treatment planning in 15-20% of casesIs a way open for using MRM to definea treatment planning designed on the real patient’s diseasemore exactly than what we can do on the basis of conventional imaging?1. Fischer, Rofo 1994; 2. Orel, Radiology 1995; 3. Deurloo, Eur Radiol 2006;4. Van Goethem, Eur Radiol 2004; 5. Fischer, Radiology 1999; 6. Gatzemeyer, 1999;7. Shelfout, Eur J Surg Oncol 2004; 8. Winnekendonk, Rofo 2004; 9. Lee, Radiology 2003;10. Liberman, AJR 2003; 11. Sardanelli, AJR 2004 …

AJR, October 2004

188 MALIGNANT FOCI1009080706050403020100P

MISSED MALIGNANT FOCIMammography (n=64), MRI (n=36)Mean diameterPercentage of invasive cancers12108642010.95.6P=.033XMMR10080604020072.250.0P=.043XMMRThe difference in sensitivitybetween mammography and MRI is enhancedby the analysis of the missed foci

The Role of Breast PatternFatty breastsMixed or dense breasts100908070605040302010075n.s.Sensitivityn.s.PPVXMMR1009080706050403020100P

Meta-Analysis 2 (Contralateral)Systematic review and meta-analysis of MRI in detection of synchronouscontralateral cancers cancer not identified on conventional Imaging in 22 studiesIncremental detection rate = 4.1%- 35% DCIS (mean 7 mm)- 65% invasive (mean 9 mm)FP detection rate = 5.2%PPV 47.9%Brennan, J Clin Oncol 2009

Shared indicationsPreoperative MRI1. Newly diagnosed ILC2. Newly diagnosed BC in a high-risk woman (screening MRI?)3. Mammography/US size discrepancy >1 cm in women

ILC1. Systematic review of patients with ILC.Additional ipsilateral lesions detected with MRI in 32%contralateral lesions in 7% while surgicalmanagement was changed in 28%. In these patients,MRI showed a 93% pooled sensitivity and a highcorrelation with pathologic tumor extent.Mann et al, Breast Cancer Res Treat 20082. A two-center non-randomized retrospective studydemonstrated that …Mann et al, Breast Cancer Res Treat 2010

PREOP MRI OF ILC2 consecutive series of patients with ILC operated in 2 tertiary centers (1993-2005,1999-2005), 267 in total, stratified for preop MRI (MR+) and no preop MRI (MR-),balanced for menopausal state, HRT, family history, tumor size, concurrent DCIS andLIN, hormone and Her/2 expression, not for mean age (MR+ 56 yrs, MR- 61 yrs).MR- (n=168) MR+ (n=99) P OR (95% IC)Initial mastectomy 46% 45% 0.753Final mastectomy 59% 48% 0.098Mastectomy after BCS 23% 7% 0.013 2.6Overall re-excision 15% 5% 0.014 3.3 (1.2-8.9)Re-excision after BCS 27% 9% 0.010 3.6 (1.3-10.2)Time to final pathologyRadical initial surgery 40 22 days 38 18 days 0.436Overall 44 29 days 40 21 days 0.238P=0.002Preop MRI for ILC can reduce re-excision rateswithout increasing mastectomy rate or time tosurgery or final pathologyMann et al, Breast Cancer Res Treat 2010

Partial Breast Irradiation (PBI)Intraoperative radiotherapy (IORT) is delivered coveringthe tumor with a 1 cm margin anterior-posterior and 2cm margins laterally.Stitzenberg , Ann Surg Oncol 2007According three studies, 5–10% of patients initiallyconsidered to be candidates for PBI prove to bePBI unsuitable after MRI.Al-Hallaq, Cancer 2008Godinez, AJR 2008Tendulkar, Cancer 2009A recent consensus statement from the American Societyfor Radiation Oncology suggested the use of PBI outsidea clinical trial in some patient subgroups.Smith, Int J Radiat Oncol Biol Phys 2009

OVERDIAGNOSIS WITH PREOP MRI ?Pre-op MRICHEMO- &RADIATIONTHERAPYCured= Avoided early ipsilateral recurrences or contralateral cancers= Avoided late (within 3-4 years) ipsilat. recurrences or contral. cancers= Overdiagnosis

POTENTIAL ODBY PREOP MRI- 11% of changedipsilateral surgery- 20-40% of positivemargins ( reoperation)- Local recurrences afterBCS+RT = 5-10% at 10yrs or 9% at 20 yrs:2-3% in the first 3-4 yrscould be anticipated byMRINo OD, if this reop rate is strongly reduced by MRI. But in somecountries (eg, Italy) , reop rate is

POTENTIAL ODBY PREOP MRI- 11% of changedipsilateral surgery- 20-40% of positivemargins ( reoperation)- Local recurrences afterBCS+RT = 5-10% at 10yrs or 9% at 20 yrs:2-3% in the first 3-4 yrscould be anticipated byMRIPotential OD of ipsilateral cancers 8%

POTENTIAL ODBY PREOP MRI- 3-4% of contralateralsurgery- 0.5-1% of risk ofcontralateral cancer- 2-3% in the first 3-4 yrscould be anticipated byMRIPotential OD of contralateral cancers 0-2%

SubgroupsPatients with a potential higher anticipated benefit frompreop-MRI can be identified as those:1. with a lobular invasive cancer2. at high-risk for breast cancer (MRI screening)3. with a cancer which shows a discrepancy in size >1cmbetween mammography and sonography4. under consideration for partial breast irradiation (PBI)5. with mammographically dense breasts6. with a unilateral multifocal/multicentric cancer or asynchronous bilateral cancer at conventional imaging7. candidates to prophylactic mastectomy8. with Paget disease9. candidates to nipple sparing mastectomySardanelli F, Pathologica 2010

An uncertain patient-based perspective… (1):Therapeutic impactPreop MRI may:1. determine unnecessary wider/additional ipsilateral excision ofmalignant lesions2. determine unnecessary contralateral excision of malignant lesions3. avoid ipsilateral reoperation4. anticipate the diagnosis of contralateral cancer, thus avoiding thefuture contralateral cancer and receiving treatment for both breastsupfrontAll the combinations from bilateral advantage to bilateralovertreatment could happen, taking into account that RT/systemictherapy may cure/prevent some of the ipsilateral/contralateral cancersdetected upfront by MRI

An uncertain patient-based perspective (2):Outcome impactPreop MRI may:1. not change recurrence rate2. not change free disease survival3. not change overall survival4. reduce recurrence rate5. increase free disease survival6. increase overall survivalAgain, all the combinations could happen, taking into account thatRT/systemic therapy may cure/prevent some of theipsilateral/contralateral cancers detected upfront by MRI

HOWEVER…Rates of MRI-detected ipsilateral and contralateralcancers are probably overestimatedWe should consider a probable 8-10% and 3-4% rate,respectivelyPreop MRI performed in non-consecutive (selected) series:patients with a probable higher likelihood of ipsilateral andcontralateral cancers (e.g., dense breasts, high-risk patients,candidates to mastectomy, etc) were includedA publication bias has been also hypothesizedRCTs should solve these problems but unfortunately…

COMICEMRI (n=816)No MRI (n=807)Re-operation rate 153 (19%) 156 19%)(repeat operation, furthermastectomy within 6 months,or pathologically avoidableinitial mastectomy)OR=0.96 (CI 0.75-1.24; p=0.77)

COMICE1173 refused to participate1338 excluded for other reasons53/761 (7%) no MRI interpreted45 Centers, 107 surgeons

Old MRI technical protocol (slice thickness = 4 mm)COMICENo sensitivity/specificity analysisBut 153 scans (19%) reread (QA program):12 (8%) non compliant with the protocol5 (3%) misreported14 (9%) non compliant or misreported; 12 of them from 6 centers with lowrecruitment, accounting for 5% (n=43) of the total MRI group; 2 of them from 2centers with high recruitment, accounting for 4% (n=31) of the total MRI group.Hypothesis:15 Centers 115Mean = 7-88/5 = 1-2/y30 Centers 701Mean = 2323/5 = 5/year

COMICE… Of the 58 [MRI+] patients who underwent [an initial] mastectomy, 32had an additional biopsy, 11 did not have a biopsy, and data wereunavailable for the remaining 15 patients. Of the 16 patients whounderwent an avoidable mastectomy, 3 did and 6 did not have a biopsy,and data are missing for the remaining 7 patients …

COMICEA list of relevant limitations:1. Too many centers with low MR experience2. 77% 50-yo and older (70% postmenopausal)3. Included also density BI-RADS 1 (13%) and 24. No systematic use of needle biopsy and localization(including MR-guided procedures)5. No precise planning for translating MRI data to theoperating theatre6. Only 1.6% (13/816) of contralateral cancers detected7. “COMICE does not fully answer whether preoperative breast MRIadds benefit because recurrence and overall survival were notexamined. COMICE was designed only to look at reoperationrate”. (Morris, Lancet 2010)COMICE SHOWS WHAT HAPPPENSWITH SUBOPTIMAL USE OF MRI

Elshof et al, Breast Cancer Res Treat 2010Preoperative MRI in 690 consecutive patients planned for BCTMRI additional findings (MRAFs) managed without MR-guided procedures.Multifocal MRAFs (within a 3-cm 3D space) not sent to targeted US, typicallyleading d to BCS with larger excision.Multicentric MRAFs (outside a 3-cm 3D space) tumor and contralateral MRAFssent to targeted US: if found needle biopsy; if malignancy confirmed over aregion too large to allow BCT mastectomy.Rule: If pathology proof cannot be obtained (i.e., if targeted USfailed to find the lesion), therapy plan is not changed.141 MRAFs in 121/690 patients (18%), without pathology proof in 81/690patients (12%). 44 multicentric and contralateral MRAFs (31%) were followed-upfor at least 22 months. In no patients these unproved MRAFs turned outto be malignant.Change of surgical planning inferior to 10%=- mastectomy for 24 breasts in 23/690 patients (3.3%)- wider ipsilateral excision in 40/690 patients (5.8%)- contralateral excision in 3/690 (0.4%).Of 40 wider ipsilateral excisions, 32 (80%) were pathology confirmed.

CommentThis experience contains a golden ruleDo not convert a BCS to mastectomy on the basis ofMRI additional finding(s) not pathologically verified to be malignantand a possible misleading messageThe use of MR-guidance is not necessary in the preoperative settingMastectomy or contralateral surgery for MRI findings without needle biopsyverification of malignancy is malpractice.MR-guided biopsy should be integrated in clinical practice as it was for needlebiopsy under stereotactic guidance.Using MR-guidance, the rate of unnecessary ipsilateral wider excisions reportedby Elshof et al. (8/40 = 20%) could have been drastically reduced. Also MRguidance has limitations and some findings can be difficult or impossible to bereached. In these cases, the golden rule by Elshof et al. should be applied.Sardanelli F, Breast Cancer Res Treat 2010

RESEARCH ISSUE FOR PREOP MRI1. Dense breasts2. PR- and ER- tumors, triple negative tumors3. Involved or closed margins after BCS4. Multifocal/multicentric tumors at conventional imaging5. Paget6. Candidates to nipple sparing mastectomty7. Pregnant patients (non-contrast MRI?)8. B3 at CB or VAB9. Translation of information (knowledge?) about 3DMRI data sets from radiological environment to theoperating theater (prone vs. supine position)10. Selection of unifocal tumors for a no-RT approachSardanelli et al, Eur J Cancer 2010

REVERSE THE PARADIGM !!!TO USE PREOP-MRI TO DOWNSIZE THE TREATMENTIn favor of BCS of localized multifocal diseaseTo avoid RTin small unifocal lesions (over 50)From SENSITIVITY = TP / (TP + FN)To NPV = TN / (TN + FN)

Nakamura et al, Breast 2008

Small RCT52 patients with localized DCIS:- 24 treated using preop MRI in surgical position- 28 treated using standard preop MRI +plus mammographic hookwire markingSignificant reduction of- volume of excised tissue(27.5 versus 57.6 cm 3 , p < 0.001)- rate of reincision for positive margins(12.5% versus 39.3%, p = 0.029 )Sakakibara et al, J Am Coll Surg 2008

Shared Rules for Preop-MRIA. Women newly diagnosed with breast cancer should always beinformed of the potential risks and benefits of preop-MRI if this isunder consideration prior to therapyB. Results of preop-MRI should be interpreted taking into account CBE,mammography, US and verified by percutaneous biopsy wheneverindicatedC. MRI-only detected lesions require MR-guidance for needlebiopsy and pre-surgical localization, and these should beavailable or potentially accessible if pre-operative MRI is tobe implementedD. Total therapy delay due to preoperative MRI (including MRI-inducedworkup) should not exceed 1 monthE. Changes in therapy planning resulting from preoperative MRI shouldbe decided by a multidisciplinary TEAMSardanelli et al, Eur J Cancer 2010


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