CONSEQUENCES OF US-FNAC

Imaging of the N0 NeckIs it reliable enough to refrain from elective treatmentMichiel van den Brekel

Netherlands Cancer InstituteAmsterdam

5th Annual Irish Head & Neck Surgical Oncology Conference 2015 Dublin

www.hoofdhalskanker.info/skinsymposium

Guest of Honor: Jesus Medina

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Cervical node involvement is the most significant prognostic factor in mucosal SCCManagement of the neck should be part of a comprehensive treatment plan

Regional Metastasis

Options for the N0 NeckObservationBased on an estimated low risk of occult metastases: T1 larynxStagingCT / MRI / PETUltrasound (guided FNAC)Sentinel node biopsy TreatmentElective NDElective Radiotherapy

The N0 Neck ConsiderationsRisk of occult diseaseModality of treatment for primaryWill the neck be entered?Prognostic impact of W&S policyFollow-Up reliabilityMorbidity of neck treatmentPatient and doctor preferences

Risk of Occult MetastasisSite and size (stage) of primary tumorDepth infiltration (5 mm)Biological characteristics: gene expressionAssessment techniquepalpation imaging - SNB

US-FNACUS-FNAC

Author N StageSiteThickness NodesRecurr.Surv. Involved %Yuen 72T1, T2 N0Tongue < 3 8 0100 3-9 44 7 76 > 9 5324 66Jones 49T1, T2 N0Any oral 5 > 5 risk x 3Spiro105T1-T3 N0Tongue, 213 97FOM 3-846 83 965 65Mohit- 84T1, T2 N0FOM 1.5 2Tabatabai 1.6-3.533 3.660Urist 89T1-T4Buccal < 3221003-5.923 90 654 40Woolgar 45T1-T4Tongue, Mean 6-7mm for cases without metastasesFOM Mean 11.2mm for cases with metastasesMorton 26T1, T2 90%Fields should encompass at risk nodal groupsEfficacy of selective RT / IMRT not studiedAccuracy of staging per level never studiedAppropriate if primary treated by radiotherapy ?No histopathologyIn case ENS, Chemo-radiation / boosting more appropriate ?Once in a lifetime treatment

Regional recurrence after (s)elective neck dissectioncN0 neckAuthorYearPrimaryRTxNeck recurrencePercentagefailureMcGuirt1995FOMNone1/263.8%Spiro1996Oral cavityNone6/1525%Hosal2000AllNone6/1274%Chow1989Oral cavityNone5/638%Carvalho2000Oral/Oropharynx44%7/1544.5 %Yuen1997TongueSome3/339%BHNCSG1998Oral cavitySome6/728%DCruz2008Tongue35%9/1595.7%

Standard of care

Brazilian Head and Neck Cancer Study Group trial

Padegar NA, Gilbert RW. Selective Neck dissection: A review of evidence, Oral Oncol 2008Recommendation (Grade C).Based on review of 13 peer reviewed articles Patients with clinical N1 regional disease may safely forego dissection of level V

Neck level IIB is more commonly involved with regional metastasis and should be dissected in patients with clinical disease.

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Imaging and the Management of the N0 Neck

Risk reduction might influence managementImaging should be very sensitive for N0 neck

Metastases should be detected with minimal delayStrict follow-up should be ensuredImaging should be applicable for follow-up

MRI, US and CTRelies on morphological featuresNodal sizeCentral necrosisIndistinct nodal marginsPeripheral contrast enhancementGross extracapsular extension

22None of these characteristics are features of clinically N0 neck

Accuracy CT and MRI N0 neck NoSensitSpecifSternCT 534092FriedmanCT 686890MRI 168082MoreauCT 325086HillsamerCT 116083MRI 96683YucelMRI 205793Vd BrekelCT 864978MRI 835588RhigiCT 2560100OkuraCT1325281MRI606184

TotalCT4075382 MRI1886085

Elective neck dissection versus staging procedure

ENDObservationPost test prob.< 0.2

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Elective neck dissection versus staging procedure

ENDObservationPost test prob. > 0.2

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In 1994 Weiss et al. created a decision tree analysis and demonstrated that when the probability of occult cervical metastasis is more than 20%, the neck should be electively treated. The treatment threshold (Rx) between elective neck dissection and observation was estimated with three (ac) probabilities of survival: a = the curable probability with END and no neck recurrence, b = the curable probability with observation and with late neck metastasis,c = the curable probability with observation and no neck recurrence. Rx = (c 0.97a) (0.00376 0.0776a 0.94b + c) = 44.4%

CT misdiagnosis

Multiple nodes

NegativePositive

MRINew, more specific contast agentsParamagnetic iron particlesBetter contrast and higher resolutionSTIRDiffusion weighted MRIDetection of Occult Metastases:Possible Improvements

On the STIR image (D), the Node on the left has the same intensity as the enlarged one on the right, both being a metastasis

BJ de Bondt: Diffusion weighted MRI

PET in N0 cases

Motivation for US-FNAC

T2N0 supraglottic Non-suspect LN at CTTumor positive at US-FNAC

Sensitivity US-FNAC N0 NeckAuthorTumorN0 Neck SidesSensSpecvdBrekel (1993)HNSCC4373100Righi (1997)HNSCC3350100Takes (1998)HNSCC6448100Nieuwenhuis (2002)Oral SCC (T3-4)2371100Nieuwenhuis (2002)Oral SCC (T1-2)3725100Hodder (2000)Oral SCC (T1-4)3358100Borgemeester (2009) Oral SCC (T1-2)3718100Borgemeester (2009)HNSCC (T3-4)12839100

MEERDERE ONDERZOEKEN GEDAAN NAAR NAUWKEURIGHEID VAN DE US-FNAC.

SPEC. IN ALLE ONDERZOEKEN 100%

SENS. VERSCHILT AANZIENELIJK

DIT ONDERZOEK IS TER HEREVALUATIE VAN DE US-FNAC VOOR STADIERING VAN DE KLINISCHE N0 HALS

US-FNA pitfallsMisses retropharyngeal, paratracheal nodes.Operator dependentCan only aspirate nodes > 3-4mmMajority of nondiagnostic samples are from nodes < 5mmLocation difficuly:Dificult locating exact nodal location for surgeon / RTDifficulty correlating with cross sectional imagingDifficulty correlating with followup US.

38However, none of these imaging technigues are able to beat the golden standdard = histological staging.Sensitivity and specificity are characteristics of the studypopulation, but not of the test itself!! Thus cant extrapolate N1 US resulst to N0 population.

Sensitivity versus radiologist

RadiologistNeck sides examinedHP positiveSensitivity (%)139119229142933111454431753

US-FNAC vs conventional imaging meta-analysis

De Bondt et al. Eur. J. Radiol. 2007

40However, none of these imaging technigues are able to beat the golden standdard = histological staging.Sensitivity and specificity are characteristics of the studypopulation, but not of the test itself!! Thus cant extrapolate N1 US resulst to N0 population.

Sentinel node

Term described in 1961 in parotid carcinoma (Gould et al.)First described as a staging tool in penile cancers (Cabanas 1977).Popularized by Morton (Melanoma) and Krag (breast cancer) in 1992 and 1993.

Conventionele methodePeritumorale injectie radiotracerLymfoscintigrafieDynamische beeldenSequentile statische opnamenMarkeren SNExcisie SNGamma detectie probePatent blauw

Nadelen huidige beeldvorming

Hoofd/hals regio:Complexe anatomieVerstrengelde lymfebanenOnverwachte / variabele drainagepatronenLastige interpretatie:Geen anatomische informatieSN bij injectiegebied worden gemist

SN procedure

SNB in HNSCCThe Evidence60+ single institution prospective trials2 multi-institutional prospective trials2 international conference consensus documents1 Meta-analysis (Paleri HN 2011)1 joint practice guidelines statementNo randomized trials

SND prospective studiesOral cavity SCCAuthorYearNecksMean SN (range)StageSens.NPVKeski2008522.1(1-5)T1-267%91% Hart2005201.5 (1-4)T1-4100%100%Payoux2005361.8 (1-3)T1-486%97%Riqual2005221.95 (1-4)T283%80%Taylor2001111.6 (1-4)T1-2100%100%Jeong2006202.55 (1-4)T1-2100%100%Stoeckli2007281.2 (1-2)T1-2100%100%Civanthos20101403 (median)T1-290%96%

Civanthos trial: NPV was 96%, False positive rate 10% overall, 10 % for tongue, 25% for FOM, and 0% for other.Because neck dissection after SND is Gamma probe guided, the neck dissection will be more accurate, and its own false negative rate (due to leaving nodes) will be lower. Thus actual SND procedure is likely better that data above.For experienced surgeons and T1 tumors, the NPV was 100%!

NPV of 95 % of SNB and thus the 5% neck failure rate cannot be compard to 5% failure after neck dissection, because this should be added to the case. It basically means that SNB has a 5% higher rate of failure than neck dissection. At teh same time, the neck dissection specimens in SNB studies were scrutinized mpore diligantly for metastatic disease.

THE NPV varies between 88% and 100% across studies

SND alone and long term follow upOral cavity SCCAuthorYearNStageFU (months)Sens.NPVSalvageFrerich200750T1-328 (7.2-49.5)80%94%50%Stoeckli200751T1-219 (3-40)91%94%100%Alkureishi201072T1-2> 6590%95%-Pezier201260T1-222 (0.26-53)94%97%100%

SNB: no nerve complicationsDie 6% neck failure is the negative predictive value!!

Methode9 patinten: 6 mondbodem, 3 tongPeritumorale injectie radiotracerConventionele beeldvormingHybride SPECT-CT*Intra-operatief:Gamma probeMini gamma camera**

*SymbiaT, Siemens, Erlangen, Duitsland** Sentinella, Gem Imaging, Valencia, Spanje

Fluorescence

Arguments against SNB procedureMultiple sentinel nodesComplicated processOrganisationLearning curveLimited applicability in HNSCCT1/T2 oral cavityT1 oropharyngealT1 supraglottic larynxFree flap necessityNasty recurrences

Prognostic Impact Wait & SeeDepends on salvage rate of neck metastasestreatment delaymetastatic rate of the lymph node metastases

Study: decrease treatment delay by regular USFNAC follow-up after transoral excision

Wait & See and PrognosisKligerman3333%27%Ho2836%30%Fakih4057%30%Cunningham4342%50%McGuirt10336%59%Vandenbrouck3647%82%TOTAL28341%50%van den Brekel7718%71%

PtsN+salvagedNieuwenhuis161 21% 79%PalpationUSFNAC

Elective neck dissection versus observation

Fasunla el al Oral Oncology 2011

55This means that patient who wants to be observed needs to realize that chance of ultimate failure is less than 2 fold compared to END (het is 1.7 fold). This is highly sgnificant, but how clinically relevant? Based on clinical examination follow up.Elective treatment gives 5-7% failure, observation gives 30&% failure, 50% of which can be salvaged, thus 15% failure with clinical palpation. With USFNAC this may be better!!! Maar belangrijk punt: END grop kan ook zeker 50% gesalvaged worden.Overall conclusion: clinical observation is inferieur. Maar later na imaging zeg ik dat USFNAC may be okay.

Survival NKI5-year survival in W&S oral cavity (T1-2) is 79%. 5-year survival in END oral cavity(T2) is 75%.

VERWIJZEN NAAR DE GRAFIEK!!!!

Okura 2009 (http://cdn.intechopen.com/pdfs-wm/28960.pdf)

ConclusionsNo difference in survival between W&S and END if follow-up is very strict

The incidence of occult LNM is very high in oral cancer, even T1

The sensitivity of imaging in these small tumors is quite low (18-25%)

Policy of US-FNAC to select for a W&S policy is disputable..

SN biopsy might be more accurate than imaging but less than END, role unclear

56% BIJ DE END GROEP IN TEGENSTELLING TOT 69% BIJ DE W&S GROEP!!!! Deze getallen verschillen ook niet significant van elkaar.Door kleine aantallen kan je hier weinig over zeggen