1

1
1,200
75




268/1610400

:0-2354-70252205

:0-2644-9097

ISBN 978-974-422-715-7

37310700
.0-2424-8715.0-2879-7082

organpreservation2.5
(Hypopharynx)1(
vol5,2001-2003)

(Multidisciplinary approach)

NationalComprehensive
CancerNetwork(NCCN)2011

2557

ClinicalpracticeGuideline

Flowchart
Supraglotticcancer
Glotticcancer
Hypopharyngealcancer

1
2
12
19

(Laryngeal cancer)
(Hypopharyngeal cancer)

25

28

33

35

36

38

43

49

68

(CategoriesofConsensus)

2(strengthofevidence)
(consensus)

1

2A

2B

1:(randomized
clinicaltrialsmeta-analysis)

2A:1
(phaseIICohort
retrospectivestudies)

2B: 12A

2B
1
3:
32
randomizedtrial
3
2A

 H&P including a complete head and neck

mirror and fiberoptic examination as clinically
indicated
Biopsy
Chest imaging
CT with contrast and thin cuts through and/or
MRI of primary and neck
Consider PET-CT for stage III-IV disease
Examination under anesthesia with endoscopy
Preanesthesia studies
Dental evaluation as indicated
Nutrition,speech & swallowing
evaluation/therapy, and audiogram as indicated
Consider videostrobe for select patients
Multidisciplinary consultation as indicated

Workup

See Treatment of Very

Advanced Head and Neck
Cancer (ADV-1)

T4b, any N or
Unresectable nodal
disease

See Treatment of Primary

and Neck (SUPRA-3)

T4a, N0

See Clinical Staging

(SUPRA-4)

See Treatment of Primary

and Neck (SUPRA-2)

T3, N0
Requiring total
laryngectomy

Node positive disease

See Treatment of Primary

and Neck (SUPRA-1)

Most T1-2, N0
Not requiring total
laryngectomy

Clinical staging

Supraglotticcancer

Definite RT (T1, T2)

(patient unfit to Sx or
want to avoid Sx)

or

Open partial laryngectomy

(OPL) or SCPL or Near total
laryngectomy ND (T2, T3)

or

Endoscopic resection neck

dissection (T1, T2)
(If T2, followed by RT)
RT
Chemo/
RT(consider)

Chemo/ RT
RT(for selected
patient)

Positive node >1 or

other adverse feature
Adverse feature node
(extracapsular nodal spread
or positive margin)

Observe
RT (consider)

Adjuvant treatment

One positive node and/or no

adverse feature node

Node negative

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T1-2, N0
(selected T3)
(No subglottic or
post cricoids
involvement)
(Not require TL)

Clinical staging

SUPRA 1

Induction chemo
(category 3)

or

Definite RT
(If patient not candidate for Sx
or concurrent chemo/RT)

or

TL

or

TL thyroidectomy with
Ipsi or bilat prophylactic
neck dissection

or

Adverse feature node

(extracapsular nodal spread
or positive margin)

Positive node>1 or
other adverse feature

Node negative
One positive node and/or no
adverse feature node

RT

RT
RT or
chemo/RT
(consider)
Chemo/RT
RT (for selected
patient)

RT

Primary site:
Salvage surgery Neck dissection
Residual
tumor

Adjuvant treatment

See Response After Induction

chemotherapy

Concurrent systemic
therapy/ RT
Cisplatin preferred (category 1)

Primary site:
complete
clinical
response

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T3, N0
(post cricoids
involvement)
(requiring TL)

Clinical staging

SUPRA 2

Induction chemo
(category 2B)

or

Concurrent chemo RT

or

SCPL or TL
thyroidectomy with
Ipsi or bilat prophylactic
neck dissection

Neck dissection

RT or
Chemo/RT
(option)

Chemo/RT

Salvage surgeryNeck dissection

No residual node

Residual node

Other risk
features

Extracapsular
nodal spread
and/or
positive margin

RT

Adjuvant treatment

See Response After Induction

chemotherapy

Primary site:
Residual
tumor

Primary site:
Complete
clinical
response

Adverse
features

No adverse
features

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Contraindication of SCPL : involve arytenoids, cricoid, subglottic, post commissure, hyoid,outer cortex of thyroid cartilage

T4a N0
(requiring TL)

Clinical staging

SUPRA 3

Node positive
Disease
(Any T and N+)

See Treatment of Primary

and Neck (SUPRA-6)

See Treatment of Primary

and Neck (SUPRA-7)

See Treatment of Head and

Neck Cancer (ADV-1)

T4a, N1-N3

T4b, N any, or
unresectable nodal
disease

See Treatment of Primary

and Neck (SUPRA-5)

Requiring total
Iaryngectomy
(MostT3, N2-3)

Not requiring total

Iaryngectomy
(T1-2, N+ and selected
T3, N1)

Clinical staging

SUPRA 4

Neck dissection in T1N3

(category 2b)

or

Induction chemo
(category 3)

or

Other risk
features

Extracapsular
nodal spread
and/or
positive margin

RT/CCRT

See Response After Induction

chemotherapy

Adverse
features

RT or
chemo/RT
(option)

Chemo/RT

N1 : observe or RT (option)
N2-3 : RT

Salvage surgeryNeck dissection

No residual node

Neck dissection

Adjuvant treatment
Residual node

No adverse
features

Primary site:
Residual
tumor

Open partial laryngectomy

(OPL) or SCPL/Near total
larygectomy + ND
or endoscopic (selected case)

or

Concurrent systemic
therapy/RT
cisplatin preferred
(category 1)
or definite RT
(patient unfit to Sx)

Primary site:
Complete
clinical
response

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T1-2, N+
(selected T3N1)
(No subglottic or
post cricoids
involvement)
(Not requiring
TL)

Clinical staging

SUPRA 5

Induction chemo
(category 2B)

or

SCPL or near total

Iarygectomy or TL
thyroidectomy with
Ipsi or bilat neck dissection

or

Concurrent systemic
therapy/RT
cisplatin preferred
(category 1)

Neck dissection

Chemo/RT
RT or
chemo/RT
(option)

Extracapsular
nodal spread
and/or
positive margin
Other risk
features

RT

Salvage surgeryNeck dissection

No residual node

Residual node

Adjuvant treatment

See Response After Induction

chemotherapy

Adverse
features

No adverse
features

Primary site:
Residual
tumor

Primary site:
Complete
clinical
response

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T3 N2 -N3
(requiring TL)

Clinical staging

SUPRA 6

See Response After Induction

chemotherapy

Induction chemo
(category 2B)

Neck dissection

RT or
chemo/RT
(option)

Chemo/RT

Salvage surgeryNeck dissection

No residual node

Residual node

Other risk
features

Primary site:
Residual
tumor

Primary site:
Complete
clinical
response

Adverse
features

Extracapsular
nodal spread
and/or
positive margin

RT

Adjuvant treatment

or

Concurrent chemo RT

or

SCPL or TL
thyroidectomy with
Ipsi or bilat prophylactic
neck dissection

No adverse
features

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Contraindication of SCPL : involve arytenoids, cricoid, subglottic, post commissure, hyoid,outer cortex of thyroid cartilage

T4a N1-3
(requiring TL)

Clinical staging

SUPRA 7

Primary site:
< Partial
response

Primary site:
Partial
response
(PR)

Surgery

Chemo/RT
(category 2B)

Observe

CR

Adverse
features

No adverse
features

Other risk
features

Extracapsular
spread and/or
positive margin

RT
or
Consider Chemo/RT

Chemo/RT (category 1)

RT

Salvage
surgery

Observe

No residual
tumor

Residual
disease

Neck dissection

Residual
tumor in neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Response after
induction
chemotherapy

Primary site:
Complete
response
(CR)

Definitive RT
(category 1)
or Consider
chemo/RT
(category 2B)

Response assessment

Response after induction chemotherapy

10

T4b, any N,
or unresectable
nodal disease

ADV 1

Supportive care

Palliative RT

Systemic therapy RT

11

See Treament (GLOT-1)

See Treament (GLOT-1)
See Treament of Primary
and Neck (GLOT-2)
See Treament of Primary
and Neck (GLOT-3)
See Treament of Primary
and Neck (GLOT-4)
See Treament of Very
Advanced Head and Neck
Cancer (ADV-1)

Total Iaryngectomy
not required
T3 requiring total
laryngectomy (N0-1)
T3 requiring total
laryngectomy (N2-3)
T4a disease
T4b, any N or
Unresectable nodal
disease

Treatment of primary and neck

Carcinoma in situ

Clinical staging

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

H&P including a complete head and neck

exam; mirror and fiberoptic examination as
clinically indicated
Biopsy
Chest imaging
CT with contrast and thin cuts through larynx
and/or MRI of primary and neck
Consider PET-CT for stage III-IV disease
Examination under anesthesia with endoscopy
Preanesthesia studies
Dental evaluation as indicated
Nutrition,speech & swallowing
evaluation/therapy, and audiogram as indicated
Consider videostrobe for select patients
Multidisciplinary consultation as indicated

Workup

Glotticcancer

12

Total Iaryngectomy
Not required
N0

Observe

Adjuvant treatment

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

RT
or
Partial Iaryngectomy/
Endoscopic or open
resection as indicated

Carcinoma in situ

Treatment of primary and neck

Endoscopic resection
or
RT (option)

Clinical staging

GLOT 1

13

N0

N1

Surgery

or

Primary site :
Complete
clinical
response
(N + at initial
staging)

Laryngectomy (neartotal
/total laryngectomy)
ipsilateral thyroidectomy or
bilateral thyroidectomy,
ipsilateral neck dissection or
bilateral neck dissection

Primary site :
Residual
tumor
Laryngectomy (neartotal
/total laryngectomy)
ipsilateral thyroidectomy or
bilateral thyroidectomy

RT if patient not
candidate for
systemic therapy/RT

or

Concurrent
systemic
therapy/RT
cisplatin preferred
(catagory 1)

Primary site :
Complete
clinical
response
(N0 at initial
staging)

Treatment of primary and neck

Observe

Neck dissection

Adverse
features

No adverse
features

Extracapsular Chemo/RT
nodal spread (category 1)
and/or
positive margin
RT or
Other risk
consider
features
chemo/RT

RT

RT (consider)

Salvage surgery + neck

dissection as indicated

No residual node

Residual node

Adjuvant treatment

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T3 requiring
total Iarygectomy
(N0-1)

Clinical staging

GLOT 2

14

Induction chemotherapy
(category 3)

Surgery

Primary site :
Residual
tumor

Adverse
features

No adverse
features

Extracapsular Chemo/RT
nodal spread
(category 1)
and/or
positive margin
RT or
Other risk
consider
faetures
chemo/RT

RT

Observe

Neck dissection

Salvage surgery + neck

dissection as indicated

No residual
tumor in
neck

Residual tumor
in neck

Adjuvant treatment

See Response After Induction

chemotherapy

Laryngectomyipsilateral
thyroidectomy or bilateral
thyroidectomy with
ipsilateral neck dissection
or bilateral neck dissection

Concurrent
systemic
therapy/RT
cisplatin preferred
(category 1)

Primary site :
Complete
clinical
response

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T3 requiring
total Iaryngectomy
(N2-3)

Clinical staging

GLOT 3

15

Primary site :
< Partial
response
Surgery
Adverse
features

Other risk
features

Extracapsular
spread and/or
positive margin

Salvage
surgery

Residual
disease

RT
or
Consider chemo/RT

Chemo/RT (category 1)

RT

Observe

CR

Observe

No residual
tumor in neck

No adverse
features

Chemo/RT
(category 2B)

Primary site :
Partial
response
(PR)

Neck dissection

Residual
tumor in neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Response after
induction
chemotherapy

Definitive RT
(category 1)
or Consider
chemo/RT
(category 2B)

Primary site :
Complete
response
(CR)

Response assessment

Response after induction chemotherapy

16

Surgery

Consider concurrent
chemoradiation
Primary site :
Residual
tumor

Negative

Observe

Neck dissection

RTchemotherapy

Salvage surgery + neck

dissection as indicated

No residual
tumor in
neck

Residual tumor
in neck

N2-3
Primary site :
Complete
clinical
response

Total laryngectomy with ipsilateral

thyroidectomy, unilateral or bilateral
neck dissection

N1

Total laryngectomy with ipsilateral

thyroidectomy unilateral or bilateral
prophylactic neck dissection

Adjuvant treatment

Total laryngectomy with ipsilateral

thyroidectomy
ipsilateral or contralateral neck dissection

N0

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Selected T4a,
patients who
decline surgery

T4a,
Any N

Clinical staging

GLOT 4

17

T4b, any N,
or unresectable
nodal disease

ADV 1

Supportive care

Palliative RT

Systemic therapy RT

18

 H&P including a complete head and neck

mirror and fiberoptic examination as clinically
indicated
Biopsy
Chest imaging
CT with contrast and thin cuts through and/or
MRI of primary and neck
Consider PET-CT for stage III-IV disease
Examination under anesthesia with endoscopy
Preanesthesia studies
Nutrition,speech & swallowing
evaluation/therapy, and audiogram as indicated
Dental evaluation
Consider videostrobe for select patients
Multidisciplinary consultation as indicated

Workup

T4b, any N or
Unresectable nodal
disease

Advanced cancer
requiring
pharyngectomy with
total laryngectomy

Most T1,
N0, selected T2, N0
(not requiring total
Laryngectomy)

T4, Any N

T1, N+;
T2-3, Any N

Clinical staging

See Treatment of Very

Advanced Head and Neck
Cancer (ADV-1)

See Treatment of Primary

and Neck (HYPO-3)

See Treatment of Primary

and Neck (HYPO-2)

See Treatment of Primary

and Neck (HYPO-1)

Hypopharyngealcancer

19

Adverse
features

No adverse
features

Primary site :
Residual
tumor

Surgery : Partial
larygopharyngectomy
(open or endoscopic)
+ ipsilateral or bilateral
neck dissection

or

Definitive RT

Primary site :
Complete
clinical
response

Perineural invasion
Vascular invasion

Positive margin

RT
or
consider
chemo/RT

Re-excision or
Chemo/RT

Chemo RT
(category 1)

Adjuvant treatment

Salvage surgery
+ neck dissection
as indicated

Extracapsular
nodal spread
positive margin

Treatment of primary and neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T1 N0
selected T2N0
(Not requiring TL)

Clinical staging

HYPO 1

20

Laryngopharyngectomy
+ neck dissection
including level VI

Neck dissection
Observe

Residual tumor
In neck
No residual
tumor in neck

See Response After

Induction chemotherapy

Salvage surgery + neck

dissection as indicated

RT or consider
chemo/RT

Chemo RT
(category 1)

Other risk
features

Extracapsular
nodal spread
and/or
positive
margin

Adjuvant treatment

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Induction
chemotherapy

Primary site :
Residual
tumor

Primary site :
Complete
clinical
response

Adverse
features

No adverse
features

Treatment of primary and neck

T1N+; T2-3, Any N

or
(requiring
pharyngectomy with
total laryngectomy)
Selected T2N0
Concurrent systemic
therapy/RT

Clinical staging

HYPO 2

21

Primary site :
< Partial
response
Surgery
Adverse
features

Other risk
faetures

Extracapsular
spread and/or
positive margin

Salvage
surgery

Residual
disease

RT
or
consider chemo/RT

Chemo/RT (category 1)

RT

Observe

CR

Observe

No residual
in neck

No adverse
features

Chemo/RT
(category 2B)

Primary site :
Partial
response
(PR)

Neck dissection

Residual
tumor in neck

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

Response after
induction
chemotherapy

Definitive RT
(category 1)
or Consider
chemo/RT
(category 2B)

Primary site :
Complete
response
(CR)

Response assessment

Response after induction chemotherapy

22

Concurrent systemic
therapy/RT
(category 3)

or

Primary site :
Residual
tumor

Primary site :
Complete
clinical
response

Observe

Neck dissection

Salvage surgery + neck

dissection as indicated

No residual
tumor in neck

Residual tumor
In neck

Chemo/RT

Adjuvant treatment

Follow-up

Adverse feature: extracapsular nodal spread, positive margin, pT4 primary, N2 or N3 nodal disease, perineural invasion, vascular embolism

T4a,
Any N

Treatment of primary and neck

Laryngopharyngectomy neck dissection

(prefered)

Clinical staging

HYPO 3

23

T4b, any N,
or unresectable
nodal disease

ADV 1

Supportive care

Palliative RT

Systemic therapy RT

24

25

(Larynx)
(Hypopharynx)

..2536 .. 2539 ..2542 .. 2545 .. 2549

3.3 0.4 3.1 0.3 2.7 0.4 2.5 0.3 2.7 0.4
()

1.6 0.2 1.2 0.2 1 0.2 1 0.2 1.2 0.2

()

WHO..2551
8.3
2.7

26

CancerinThailand2549
5.52.5
1.10.4
(2549)

(2549)

27

28

laryngealcancerhypopharyngealcancer

1.
2. fiberoptic rigidendoscope laryngoscopy,
bronchoscopyesophagoscopy

3.

TNMstaging
1. primarylesion
a. endoscope
b. CTscanMRI
i. CT/MRI
20upstaging(1-2)
stagingCT/MRI
localfailurecausespecificsurvivalrate(1)
CT/MRI
partial
laryngectomycurative
radiationCT/MRI

29

ii. CTMRIMRI
prevertebraltissueinvasionintralaryngealspaceinvasion
CTscancartilageinvasion

2.
a.
b. CT/MRI
i.CT/MRI
(resectability)
ii. CT/MRIultrasound
electiveneckdissection
electiveneckdissection
CT/MRIultrasound
3. distantmetastasis
distantmetastasislaryngealcancerhypopharyngealcancer
4-242-17(45-83)
(10-41)(6-24) distantmetastasis
a. LungmetastasisCTchestlungmetastasis
plainfilmchestx-ray(3-4)screeningtest(5)
distantmetastasis5-yearoverallsurvival
distantmetastasis1252(6)
distantmetastasisoverall
survival(6)CTchest
plainfilmchestx-raylungmetastasis
lowernecknodeenlargementextralaryngealinvasion
b. Bonemetastasisalkalinephosphatasebonescan
bonescan
c. Livermetastasis
sensitivity45specificity

30

75UltrasoundCTscan
U/Saccuracy
85CTscan8879
4. secondprimarytumor
secondprimarytumor
80(7)(3yearsurvival58second
primarytumor30secondprimarytumor)(8)
laryngealcancersecondprimarytumor
hypopharyngealcancer(8)secondprimarytumor

1. plainfilmchestx-rayCTchest
2. Esophagoscopyhypopharyngealcancer
PET-CTprimarylesion,distantmetastasissecond
primarytumor CT/MRI

recurrenttumoredemafibrosis

1. CBC,
bloodsugar,BUN,creatinine,electrolyte,liverfunctiontest,UA,filmchest,EKG
2. (
)
3.
4. ()
5 (
)

31

1. (highly
recommend) fiberopticendoscope(optional).
2. rigidendoscopedirectlaryngoscope
(recommend),bronchoscope(consider),esophagoscopehypopharyngeal
cancer(recommend), fiberopticendoscope(optional).
3. (highlyrecommend)
4. plainfilmchestx-ray(highlyrecommend)
5. CTchest(considerifindicate)
6. CT/MRIprimary(consider)
7. CT/MRInecknodemetastasis(consider)
8. ultrasoundneck+/-fineneedleaspiration(consider)
9. ultrasoundliver(consider)
10. bonescan(consider)
11. preanesthesiastudies(recommend)
12. dentalevaluation(recommend)
13. nutritionalevaluation(recommend)
14. speechandswallowingevaluation(consider)
15. audiogram(consider)
16. PET-CT primary,distantmetastasis,secondprimarytumor (consider)

32

Reference:
1. BarberaL,GroomePA,MackillopWJ,etal.TheroleofcomputedtomographyintheTclassificationof
layngealcarcinoma.Cancer2001,91;2:394-407.
2. KimJW,YoonS-Y,ParkI-S,etal.Correlationbetweenimagesandpathologicalresultsinsupraglottic
cancer.Thejournaloflaryngology&otology2008,122:1224-1229.
3. FerlitoA,BuckleyJG,RinaldoA,etal.Screeningteststoevaluatedistantmetastasesinheadandneck
cancer.ORL2001,63:208-211.
4. RemcodeBree,DeurlooEE,SnowGB,etal.Screeningfordistantmetastasesinpatientswithheadandneck
cancer.Laryngoscope2000,110:397-401.
5. JackelMC,ReischlA,HuppertP.Efficacyofradiologicscreeningfordistantmetastasesandsecond
primariesinnewlydiagnosedpatientswithheadandneckcancer.Laryngoscope2007,117:242-247.
6. HaerleSK,SchmidD.T.,AhmadN,etal.Thevalueof18F-FDGPET/CTforthedetectionofdistant
metastasesinhigh-riskpatientsWithheadandnecksquamouscellcarcinoma.OralOncology2011,47:653-659.
7. StrobelK,HaerleSK,StoeckliSJ.Headandnecksquamouscellcarcinoma(HNSCC)-Detectionof
synchronousprimarieswith18F-FDG-PET/CT.EurJNuclMedMolImaging2009,36:919-927.
8. ChuP-Y,ChangS-Y,HuangJ-L,etal.Differentpatternsofsecondprimarymalignancyinpatientswith
squamouscellcarcinomaoflarynxandhypopharynx.AmericanJournalofOtolaryngologyHeadandNeck
MedicineandSurgery2010,31:168174.
9. SchreveR.H.,TerpstraO.T.,AusemaL.,LamerisJ.S.,VanSeijenA.J.JeekelJ.Detectionofliver
metastases.Aprospectivestudycomparingliverenzymes,scintigraphy,ultrasonographyandcomputed
tomography.BritishJournalofSurgery,1984;Dec;71(2):947-949doi:10.1002/bjs.1800711212
10. LinebergerComprehensiveCancerCenterBiostatisticsCore,UniversityofNorthCarolina,ChapelHill,North
Carolina,USA.Otolaryngology--headandNeckSurgery:OfficialJournalofAmericanAcademyof
Otolaryngology-HeadandNeckSurgery[2012;146(1):88-91]

33

(LaryngealcancerandHypopharyngealcancer)

(Surgery)

primaryEndoscopicresection,openpartial
laryngectomyTotallaryngectomyextensionoflesion
T4
Totallaryngectomy

neckdissection lymphnode
comprehensiveneckdissection

(N0)selectiveneckdissection
levelII-IV (T3,T4)

(Adjuvanttherapy)

1. Postoperationchemoradiation()

- Recommend
o Positivemargin,
o Extracapsularnodalspreadoftumor
- Consider
o pT3orpT4
o N2orN3
o Perineuralinvasion
o Vascularembolism

34

2. Postoperationradiation(StageIII,IV)
3.

(concurrent
chemoradiation)

Inductionchemotherapy
completeresponseInduction
chemotherapy
Induction
chemotherapypartialresponse
Inductionchemotherapy

(PalliativeTreatment)

35

(SurveillanceandFollowup)

1.
1 1-3
2 2-4
3-5 4-6
5
6-12
2. 1
3. Thyroidfunctiontestlaryngectomy

hypothyroidism
6
4.

36

(Managementofrecurrentlaryngealcancerandhypopharyngealcancer)
:biopsygold
standard
chemoradiationpersistentrecurrent

8-12
edemafibrosis

Directlaryngoscopeandbiopsyunder
generalanesthesia
CTscan,PETCT
persistentandrecurrent

1.

positivemargin adjuvant chemoradiation

()
2.
adjuvanttreatment
()
3.
()
4.
()

TREATMENT OF HEAD AND NECK CANCER

DIAGNOSIS

Surgery

Locoregional
recurrence
without
prior RT

Recurrent
or
Persistent
disease

37

Locoregional
recurrence or
Second primary
with prior RT

Resectable

or

No adverse
featurese

Adverse
featurese

Chemo/RT

Observe
Extracapsular
spread and/or
positive margin

Chemo/RT
(category 1)

Other risk
features

RT
or
Consider chemo/RT
Salvage therapy for
persistent disease
as indicated

Unresectable

Best supportive care

Palliative chemotherapy/RT

Resectable

Surgery reirradiation
chemotherapy, clinical trial preferred

Unresectable

Reirradiation chemotherapy, clinical trial preferred

or
Chemotherapy (see distant metastases pathway)

Clinical trial preferred

Distant
metastased
Standard
therapyb

PS 0-1

Combination chemotherapy
or
Single-agent chemotherapy

PS 2

Single-agent chemotherapy
or
Best supportive care

PS 3

Best supportive care

Chemotherapy,
clinical trial preferred
or
Best supportive care
Best supportive care

PS = Performance Status (ECOG)

CTscanprimaryCTchest

Totallaryngectomypersistent:tumor
chemo/radiation
tumornormaltissuearea
0.5-1
tumormargin0.5-1

Recurrent:tumorcompleteresponsetumor
6 margin0.5-1
frozensectionmarginreconstruction
frozensection

38

(Rehabilitationinlaryngealcancerpatientsundergoingtotallaryngectomy)

(laryngealconservationsurgery)
(concurrentchemoradiationtherapy)
(totallaryngectomy)


(salvagetotallaryngectomy)

1. (soundsource)
2. (powersource)
3. (articulation)

1.(tracheoesophagealspeech)
(prosthesis)
2.(esophagealspeech)
3.(electrolarynx)

39

1.(tracheoesophagealspeech)

(one-wayvalve)

(primarytracheoesophagealpuncture)(secondary
tracheoesophagealpuncture)

TEP
-
-
- (devise)
- TEP

1.
2.
3.
4.
2.(esophagealspeech)

65Hertz

40

(
26-40)Gate-Ryan,Salmon

-
-
-
3.(electrolarynx)

(neckplacementdevice)

(monotone)

- (TEshunt)
-
-
-

41

Reference:
1. Alam,DS,VivekPP,KmiecikJ.Comparisonofvoiceoutcomesafterradialforearmfreeflapreconstruction
versusprimaryclosureafterlaryngectomy.Otolaryngology-HeadNeckSurgery2008;August;139(2):240244.doi:10.1016/j.otohns.2008.03.024.
2. FaganJJ.Tracheoesophagealspeechinadevelopingworldcommunity.ArchotolaryngolHeadNeck
Surgery2002;128(1):50-53.doi:10.1001/archotol.128.1.50.
3. GadepalliC,DeCassoC,SilvaS,LoughranS,HomerJJ.Functionalresultsofpharyngo-laryngectomyand
totallaryngectomy:acomparison.TheJournalofLaryngologyandOtology.2011;August26:1-6.doi:10.1017/
S0022215111002313.
4. Gates,GA,WRyan,JCCooperJr,GFLawlis,ECantu,THayashi,ELauder,RWWelch, andEHearne. 1982.
Currentstatusoflaryngectomeerehabilitation:I.Resultsoftherapy.AmericanJournalofOtolaryngology
3(1)(February):1-7.
5. MillerS.Theroleofthespeechlanguagepathologistinvoicerestorationaftertotallaryngectomy.CA. ACancer
JournalforClinicians.1990;May1;40(3):174-182.doi:10.3322/canjclin.40.3.174.
6. PapadasT,CharokoposN,KaramouzisMV,PierakeasC,SymeonidiM,EconomouG,etal.Rehabilitation
afterlaryngectomy:Apracticalapproachandguidelinesforpatients.JournalofCancerEducation2002;17(1):
37-39.doi:10.1080/08858190209528790.
7. SalmonSJ.Adjustingtolaryngectomy.InCurrentStrategiesofRehabilitationoftheLaryngectomized
Patient:SeminarsinSpeechandLanguage.NewYork:Thieme.1986.
8. SingerS,MerbachM,DietzA,SchwarzR.PsychosocialDeterminantsofSuccessfulVoiceRehabilitation
AfterLaryngectomy.JournaloftheChineseMedicalAssociation2007;October;70(10):407-423.doi:10.1016/
S1726-4901(08)70030-3.
9. WardE.C.Differentialmodesofalaryngealcommunicationandlong-termvoiceoutcomesfollowingpharyngolaryngectomyandlaryngectomy.Foliaphoniatricaetlogopaedica.2003;55(1):39-49.
10.WilliamsSE,KohSK,FrisbyJ,HodgeR.Speakingproficiencyvariationsaccordingtomethodofalaryngeal
voicing.TheLaryngoscope1987;June;97(6):737-739.
11.XiS.Effectivenessofvoicerehabilitationonvocalisationinpostlaryngectomypatients:asystematicreview.
InternationalJournalofEvidence-BasedHealthcare2010;December;8(4):256-258.doi:10.1111/j.17441609.2010.00177.x.

42

43

4
1. (adjuvant
concurrentchemoradiation)
2.
(concurrentchemoradiation)
3. (inductionchemotherapy)
4. (palliativechemotherapy)
1.
(adjuvantconcurrentchemoradiation)
2(1-2)
(adjuvantconcurrentchemoradiation)
EORTC(1)

(extracapsularextension),(margin
positive),T3T4N2N3,
(perineuralinvasion)
(vascularembolism)subgroupanalysis
(extracapsularextension)/(margin
positive)
cisplatin100mg/m23
1,22,43

44

2.
(concurrentchemoradiation)
-

RTOG91-11(3)3(1)induction cisplatin/5FU
(2)concurrentchemoradiationcisplatin(3)
stageIIIIV T1T4concurrentchemoradiation
2
3

1
- T1N+,T2-3anyN
( laryngectomyinduction
chemotherapytripletchemotherapy)
3
2A
- T4b

performancestatus0-1(performancestatus2)

1
cisplatin100mg/m23
1,22,43
3. inductionchemotherapy
: RTOG91-11(3) induction
chemotherapycisplatin/5FU
docetaxel(4-6)paclitaxel(7)cisplatin/5FU
(TPF3
(laryngealpreservationrate)

45

inductiontripletcombination
TPF
induction
chemotherapy
inductionchemotherapy

2A
:
totallaryngectomy
inductionchemotherapy
3inductionchemotherapycisplatin/5FU
docetaxel(4-6)paclitaxel(7)cisplatin/5FU(TPF)+/-cisplatin
3larynx
preservation3
(totallaryngectomy,inductionchemotherapy)

inductionchemotherapytripletcombination
(complete
response)(partialresponse)

(<partialresponse)

(
)
inductionchemotherapy
cisplatin(100mg/m 2)3

46

inductionchemotherapy
totallaryngectomy(larynxpreservation)T1N+,T2-3anyN
2A
(T4b)

inductionchemotherapy
phaseII/III
inductionchemotherapy(TPFPF)

(8)

inductionchemotherapy
(T4b),

3
4. (palliativechemotherapy)

(locoregionalrecurrence)
(distantmetastasis)
(palliativechemotherapy)
ECOGperformancestatus0-2
(mediansurvival)6120%
(singleagentchemotherapy)
(combinationchemotherapy)combinationchemotherapy
(overallsurvival)(9)
platinum(cisplatincarboplatincisplatin)
5-FUtaxanepaclitaxelcisplatin
cisplatin/5-FU
(10)

47

cisplatin
epidermalgrowthfactorreceptor(EGFR)cetuximab(antiEGFR
monoclonalantibody)12-14%26%cisplatin
cetuximabcisplatincarboplatin5-FU
cetuximab
(medianoverallsurvival
10.17.4,hazardratio=0.8,95%CI0.64to0.99,p=0.04)
cetuximab(sepsis)(p=0.02)
(11)

(ECOGperformancestatus0-2)
palliativechemotherapyplatinum5-FU

2A

48

Reference:
1. BernierJ,DomengeC,OzsahinM,MatuszewskaK,LefbvreJL,GreinerRH,etal.EuropeanOrganization
forResearchandTreatmentofCancerTrial22931.Postoperativeirradiationwithorwithoutconcomitant
chemotherapyforlocallyadvancedheadandneckcancer.NEnglJMed.2004May;350(19):1945-52.
2. CooperJS,PajakTF,ForastiereAA,JacobsJ,CampbellBH,SaxmanSB,etal.RadiationTherapyOncology
Group9501/Intergroup.Postoperativeconcurrentradiotherapyandchemotherapyforhigh-risksquamous-cell
carcinomaoftheheadandneck.NEnglJMed.2004May6;350(19):1937-44.
3. ForastiereAA,GoepfertH,MaorM,PajakTF,WeberR,MorrisonW,etal.Concurrentchemotherapyand
radiotherapyfororganpreservationinadvancedlaryngealcancer.NEnglJMed.2003Nov27;349(22):2091-8.
4. VermorkenJB,RemenarE,vanHerpenC,GorliaT,MesiaR,DegardinM,etal.EORTC24971/TAX323
StudyGroup.Cisplatin,fluorouracil,anddocetaxelinunresectableheadandneckcancer.NEnglJMed.
2007Oct25;357(17):1695-704.
5. PosnerMR,HershockDM,BlajmanCR,MickiewiczE,WinquistE,GorbounovaV,etal.TAX324StudyGroup.
Cisplatinandfluorouracilaloneorwithdocetaxelinheadandneckcancer.NEnglJMed.2007Oct25;357(17):
1705-15.
6. PointreauY,GaraudP,ChapetS,SireC,TuchaisC,TortochauxJ,etal.Randomizedtrialofinduction
chemotherapywithcisplatinand5-fluorouracilwithorwithoutdocetaxelforlarynxpreservation.JNatlCancer
Inst.2009Apr1;101(7):498-506.
7. HittR,Lpez-PousaA,Martnez-TruferoJ,EscrigV,CarlesJ,RizoA,etal.PhaseIIIstudycomparingcisplatin
plusfluorouraciltopaclitaxel,cisplatin,andfluorouracilinductionchemotherapyfollowedbychemoradiotherapy
inlocallyadvancedheadandneckcancer.JClinOncol.2005Dec1;23(34):8636-45.
8. HittR,GrauJ,Lopez-PousaA,BerrocalA,Garca-GironC,BelonJ,etal.RandomizedphaseII/IIIclinicaltrial
ofinductionchemotherapy(ICT)witheithercisplatin/5-fluorouracil(PF)ordocetaxel/cisplatin/5-fluorouracil
(TPF)followedbychemoradiotherapy(CRT)vs.crtaloneforpatients(pts)withunresectablelocallyadvanced
headandneckcancer(LAHNC)JClinOncol.2006ASCOAnnualMeetingProceedings(Post-MeetingEdition).
vol24,No18S(June20Supplement),2006:5515.
9. ForastiereAA,MetchB,SchullerDE,EnsleyJF,HutchinsLF,TriozziP,etal.Randomizedcomparisonof
cisplatinplusfluorouracilandcarboplatinplusfluorouracilversusmethotrexateinadvancedsquamous-cell
carcinomaoftheheadandneck:ASouthwestOncologyGroupStudy.JClinOncol.1992Aug;10(8):1245-51.
10. GibsonMK,LiY,MurphyB,HussainMHA,DeContiRC,EnsleyJ,etal.RandomizedphaseIIIevaluationof
cisplatinplusfluorouracilversuscisplatinpluspaclitaxelinadvancedheadandneckcancer(E1395):anintergroup
trialoftheEasternCooperativeOncologyGroup.JClinOncol.2005May20;23(15):3562-67.
11. VermorkenJB,MesiaR,RiveraF,RemenarE,KaweckiA,RotteyS,etal.Platinum-basedchemotherapyplus
cetuximabinheadandneckcancer.NEnglJMed2008Sep11;359:1116-27.

49

(Larynx)(Hypopharynx)
(Trachea)
9

1(Epiglottis),2 (Thyroid
cartilage),3(Cricoidcartilage),4-5
(Arytenoidcartilages),6-7(Corniculatecartilages)8-9
(Cuneiformcartilages)
(Truevocal cord),(Falsevocalcord),
(Aryepiglotticfold),Pre-epiglotticspace(
),Paraglotticspacessubglottis
(1cricoid
)
1:larynx
Larynx
Cartilage

Mainstructuresandfolds
Space

Epiglottis
Thyroidcartilage
Cricoidcartilage
Arytenoidcartilages
Corniculatecartilages
Cuneiformcartilages
Truevocalcords
Falsevocalcords
Aryepiglotticfolds
Pre-epiglotticspace
Paraglotticspaces
Subglottis

50

(Laryngectomy
specimen)(Thyroidgland),(Parathyroidglands),Subglottis
Subglottis Subglottis (Prelaryngeal(Delphian)lymphnode),vallecula
1-3

1:(posteriorview)coronalplanefromposteriorview

2:(anteriorview)

51

3:(posterolateralview)

4 1

10(10%bufferedformalin)
Fixation10
(Hospital
Number)
(HIV,HepatitisB,HepatitisC,
)

52

FNAcytologyspecimen
fix70%
ethylalcohol
(SurgicalPathologyRequestForm)

()
Precaution(HIV,HepatitisB,
HepatitisC,)


//
/
Partial
laryngectomy,neckdissectionspecimen(proximalsurgicalmargin)
(distalsurgicalmargin),
32

2:

Long
Lateral
Short
Superior
Double
Deep

53

L
S
D

RNA
tissueculture(Tissuebank)

1.Biopsiedspecimen
biopsy
2.Laryngectomy
A.Hemilaryngectomy
thyroidcartilage,falsetruecordsventricle
midline
B.Supraglotticlaryngectomy
ventricle (
falsecordepiglottis)
C.Totallaryngectomy
larynx(supraglottis,glottis,subglottis)
trachea
3.Neckdissection
A.Standardradicalneckdissection
cervicallymphnodeslevelIV(inferior
bordermandibleclaviclelateralbordersternohyoid
anteriorbellydigastricanteriorborder
trapezius),spinalaccessorynerve,internaljugularvein,sternocleidomastoid
musclessubmandibularglandparotidtail

54

B. Modifiedradicalneckdissection
standardradicalneckdissection
1sternocleidomastoidmuscle,spinalaccessory
nerveinternaljugularvein
C. Regional(partialselective)neckdissection
lymphnodezonemetastasis
a) Supraomohyoidneckdissection
lymphnodeszoneI,IIIII
b) Posterolateralneckdissection
lymphnodeszoneII,III,IVV
c) Lateralneckdissection
lymphnodeszoneII,IIIIV
d) Anteriorcompartmentneckdissection
lymphnodeszoneVI
D.Extendedradicalneckdissection
neckdissectionlymphnode
standardneckdissectionskinofneck,carotidartery,levatorscapulae
muscle,vagushypoglossalnerves,lymphnodesretropharyngeal,paratracheal
uppermediastinal

55

Preauricular
lymph node
Retroauricular
lymph node
Jugular chain
lymph nodes
Spinal accessory
lymph nodes
Supraclavicular
lymph nodes

Submandibular
lymphnodes
Submental
lymphnodes
Dephian
lymphnode

4:levellevelIsubmandibular submental
lymphnodes,levelII,III,IVupper,middlelowerjugularchain lymphnodes,
levelV spinalaccessorylymphnodes,levelVIDephianlymphnodes
4.FNAcytology
cervicallymphnode

1.
2.
3.
4.

5. biopsiedspecimen

56

1. ()
2.
3.
4.
(Surgicalresectionmargin)
3%aceticacid

3:

Yellow
Lateral
L
Orange
Medial
OrangeMedia
Blue
Superior

Green
Inferior

Red
Anterior
RedRostral
Black
Posterior
,Back:Black

1. Totallaryngectomy
hemilaryngectomy,supracricoidlaynryngectomy
2.
3. ulcerative,
exophytic,ulcerativeexophytic,diffusethickening
4.
checklist4
5.

57

6. pushingborder,infiltrativeborder
7. solid,solid-cystic,necroticarea,
hemorrhage

1. 1
2. 1
3. 1
4. anteriorcommissure1
5.
6. thyroidcartilage
7.

8. ()

9. Partiallaryngectomy hemilaryngectomy,
supraglotticlaryngectomy,supracricoidlaryngectomy

(6)
10. biopsiedspecimen
cassette
11. biopsiedspecimens

58

5:laryngectomyspecimen

6:hemilaryngectomyspecimen

59

checklist

4:Checklists
Cordectomy
Gross
Specimentype
Totallaryngectomy
Checklist
Right/lefthemilaryngectomy
Supraglotticlaryngectomy
Supracricoidlaryngectomy
Other(specify).
Ulcerative
Lesion
Exophytic
Ulcerativeexophytic
Diffusethickening
Other(specify)
Greatesttumor
xxcm
size
Right
Tumorlaterality
Left
Bilateral
Midline
Truevocalcord
Tumorlocation
Falsevocalcord
Subglottis
Arepiglotticfold
Epiglottis
Anteriorcommissure
Posteriorcommissure
Pyriformsinus
Vallecularrecess
Other(specify).

60

Histologic HistologicType*
checklist
tumor

Histologicgrade

Squamouscellcarcinoma
Conventional
8070/3
Acantholyticsquamouscellcarcinoma
8075/3
Adenosquamouscarcinoma
8560/3
Basaloidsquamouscellcarcinoma
8083/3
Papillarysquamouscellcarcinoma
8052/3
Spindlecellsquamouscellcarcinoma
8074/3
Verrucouscarcinoma
8051/3
Lymphoepithelialcarcinoma
8082/3
Giantcellcarcinoma
8082/3
NeuroendocrineCarcinoma
Typicalcarcinoidtumor
8240/3
Atypicalcarcinoidtumor
8249/3
Smallcellcarcinoma,neuroendocrinetype
8041/3
Combinesmallcellcarcinoma,neuroendo- 8045/3
crinetype
Malignantsalivarygland-typetumors
Mucoepidermoidcarcinoma
8430/3
Adenoidcysticcarcinoma
8200/3
Well-differentiated
Moderate-differentiated
Poorly-differentiated
Undifferentiated
Notidentified Present Indeterminate

Lymph-Vascular
Invasion
PerineuralInvasion Notidentified Present Indeterminate
Adjacentmucosa NormalDysplasia

*7

61

Proliferative squamous lesion

No atypical changes

Atypical changes
Stromal
invasion

No definite
invasion

SCC

Deeper
sections

Invasion
SCC

Bulbous
appearance

No bulbous
appearance

Recommend
excision

Benign
Squamous
proliferation

No Invasion

Reticulated
appearance
PEH

- Descriptive report
- Rebiopsy as
clinically indicated

7:squamouslesions

neckdissectionspecimen

1. Orientatespecimenanatomicallandmark
2. lymphnodelevel8
3. orientatelymphnode
4. lymphnodelevel
5. Lymphnode3.

:lymphnodelevel

62

checklist

8:lymphnodeslevel

63

5:Checklistsneckdissection
Gross
Specimentype Standardradicalneckdissection
Modifiedradicalneckdissection
Checklist
Supraomohyoidneckdissection
Posterolateralneckdissection
Lateralneckdissection
Anteriorcompartmentneckdissection
Extendedneckdissection
Sizeofthe specimen Wholespecimenxxcm
Sternocleidomastoidmusclexxcm
Jugularvein,(length)x(diameter).
Salivaryglandxxcm
Largestlymphnodexxcm
Other(specify)
Numberofnodes LevelI...nodes
LevelII..nodes
LevelIIInodes
LevelIV.nodes
LevelV..noles
LevelVI..noles
Metastatic squamouscell
in/lymphnodes,
Histologic Metastasis
cmingreatest
carcinoma
checklist
dimensionofmetastatic
adenocarcinoma
node.
Positivein
LevelI.../....nodes
LevelII../....nodes
Others(specify)
LevelIII./nodes
LevelIV./nodes
LevelV.../..noles
LevelVI../..noles
Nometastasisinalllymphnodes

64

Oruse

N0 Noregionallymphnodemetastasis
N1
Metastaticinasingleipsilaterallymphnode, 3cmor less in
greatestdimension
N2
MetastasisasspecifiedinN2a,N2b,N2cbelow
N2a Metastasisinasingleipsilaterallymphnode,more than
3cmorlessingreatestdimension
N2b Metastasisinmultipleipsilaterallymphnodes,nonemore
than6cmingreatestdimension
N2c Metastasisinbilateralorcontralaterallymphnodes,
nonemorethan6cmingreatestdimension
N3
Metastasisinalymphnodemorethan6cmingreatest
dimension
Note Midlinenodesareconsideredipsilateralnodes
PerinodalInvasion Notidentified
Present
Indeterminate
Associateddisease Granulomatousinflammation Caseous
Non-caseous

FNAcytology

FNAcytology
(2226)

FNAsmear

objective10X
objective
40X60Xoilemersion100X

65

(
)

oCytologicalnumber
o
o
o
o
o
o
o
o
o

66

o
o
o
o

o fineneedleaspiration(FNA)(terminology)
(histopathology)
5
. Benignnegativeformalignancy
benign benigntumor
salivaryglandreactivelymphnodeinflammatory
diseases TB
. Atypical/indeterminatebenigncytological
atypia
. Suspicioussuspiciousformalignancy
malignant

. Malignantpositiveformalignancy
malignant
. Unsatisfactorynon-diagnostic

67

1

Reference:
1. RosaiJ.Guidelinesforhandlingofmostcommonandimportantsurgicalspecimens.In:RosaiandAckermans
SurgicalPathology.9thed.Philadelphia:Mosby,2004;2942-3.
2. FowlerJC,FowlerMH.Intraoperativeconsultationandgrossingtechniques.In:ThompsonLDR.HeadandNeck
Pathology. 1sted.Philadelphia:ElsevierChurchillLivingstone,2006:580-93.
3. PilchBZ.Larynxandhypopharynx.In:HeadandNeckSurgicalPathology.Philadelphia:Lippincott
Williams&Wilkins.2001:230-83.
4. BarnesL.Diseasesofthelarynx,hypopharynx,andtrachea.Surgicalpathologyoftheheadandneck.3rded.
NewYork:InformaHealthcare.2009:109-200.
5. SlootwegPJ,RichardsonM.Squamouscellcarcinomaoftheupperaerodigestivesystem.GneppDR.Diagnostic
SurgicalPathologyoftheHeadandNeck.2nded.Philadelphia:WBSaunders,2009:60-4.
6. MedinaJE.Arationalclassificationofneckdissections.OtolaryngolHeadNeckSurgery1989;100:169-176.
7. RobbinsK.T.PocketGuidetoNeckDissectionandTNMStagingofHeadandNeckCancer.Alexandria,
VA:AmericanAcademyofOtolaryngologyHeadandNeckSurgeryFoundation,Inc.,1991:9-20
8. RobbinsKT,MedinaJE,WolfeGT,LevinePA,SessionsRB,RuetCW.StandardizingNeckDissection
Terminology.ArchOtolaryngolHeadNeckSurg1991:117:601-605.
9. WilliamH.Westra,M.D.,SurgicalPathologyDissection:AnIllustratedGuide,2ndEdition.NewYork:
Springer-Verlag,Inc.2003:38-42,54-57.
10. StelowEB,MillsSE.BiopsyInterpretationoftheUpperAerodigestiveTractandEar.Philadelphia:Lippincott
Williams&Wilkins:2008:17-28.
11. CytopathologyChecklistforLaboratoryAccreditationProgram:CommissiononLaboratoryAccreditation,
TheCollegeofAmericanPathologists(CAP),U.S.A.,2006
12.

68

1.
2. (PeerReviewer)
3.
4. (Radiotherapy)
5. (Chemotherapy)
6. (Pathology)

1.
2.
3.
4.
5.
6.

7.

8.
9.
10.
11.
12.

13.
14.
15.
16.

17.
18.
19.

20.

21.


22.


23.
24.
25.

69

(PeerReviewer)
1.
2.
3.
4.

70

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.

(Radiotherapy)

1.

2.
3.

4.

5.

6.

(Chemotherapy)
1.
2.
3.
4.

71

(Pathology)
1.
2.
3.
4.
5.