Head and NeHead and NeNasopharynxNasopharynx

Nancy LeD t t f R dDepartment of Rad

Memorial Sloan-Kette

eck Cancer I:eck Cancer I:x Oral Cavityx, Oral Cavity

ee, M.D.di ti O ldiation Oncologyering Cancer Centerg

Course OCourse O•Disc ss the e idence for•Discuss the evidence for

chemoradiotherapy in the

•Compare whether alteredconcurrent chemotherapfractionation with the sam

•Discuss toxicity associatyconcurrent chemoradioth

ObjectivesObjectivesr sing conc rrentr using concurrent e definitive setting

d fractionation plus y is better than standard

me chemotherapy regimen

ted with the use of herapy

Head and NHead and N• W ld id 500• Worldwide: > 500yearyear

•~ 5% of newly diad ltadults

•U.S.A. per year: >13,000 deaths

eck Cancereck Cancer0 0000,000 cases per

gnosed cancers in

> 40,000 cases and

Head and NeHead and Ne•Majority present wiMajority present wi

regionally advancedisease

•Mortality is high fordisease

•Those cured of diselong-term morbidit

eck Cancereck Cancerith locally orith locally or ed stages III or IV

r locally advanced

ease experience y

History of Locallyd N k Cand Neck Can

ResectablResectabl

•S di th•Surgery + radiotherapy

••Cosmetic and functional o

•Improvement of surgical t

•Perioperative/long-terms

• 5 year OS between 30-50%

y Advanced Head T t tcer Treatment

e Diseasee Disease

outcome can be devastatin

technique/reconstruction

sequelae remain serious

%

History of Locallyand Neck Can

UnresectabUnresectab

•Traditional treatmradiation alone as

•Results are subopResults are subopwith control rates

y Advanced Headcer Treatment

ble Diseaseble Disease

ment involves single modality

ptimal and POORptimal and POOR s < 20%

Head and NHead and N•How can we increaseadvanced resectable aadvanced resectable ahead and neck cancer

•How can we decreaseHow can we decreasemorbidity from aggresmodalities?

eck Cancereck Cancer cure rates for locally and unresectableand unresectable r?

e long-terme long-term ssive treatment

Can Local ControSurv

•Wadsley (IJROBP, 2004): Ebetween improvement in locoverall survival in 19 random

•A 10% improvement in the 2di t d t l d t 6 7% 5predicted to lead to a 6.7% 5

•Li it ti f RT i t f•Limitation of RT in terms ofcausing excessive complica

•What about chemotherapy?

l with RT Improve pival?

Establish the relationship coregional control and mized trials

2 year locoregional control is5 i i OS5 year increase in OS

f d l ti ith tf dose escalation without ations

?

RATIONALE OF COMBIAND CHEMOTHEAND CHEMOTHE

Chemothe•Perturb cell kinetics; Preferen

•S iti t ll t di•Sensitize tumor cells to radiarepopulation

•Enhance radiation induced ap

• Inhibit repair of radiation dam

••Sterilize micrometastases ou

••Decrease tumor mass leadinreoxygenation, and increase

INING RADIOTHERAPYERAPY in H/N CAERAPY in H/N CAerapy May:ntially kill hypoxic cells

ti I hibit tation; Inhibit tumor

poptosis

mage

utside the radiation field

ng to improved blood supply, ed radiosensitivity

RATIONALE OF COMBIAND CHEMOTHEAND CHEMOTHE

Radiothe

•Decrease tumor mass•Decrease tumor mass supply improved dr

•Decrease tumor mass proliferation increaproliferation increa

• Inhibit repair of drug dam

• Increase chemotherapy i

INING RADIOTHERAPYERAPY in H/N CAERAPY in H/N CAerapy May:

improved blood improved blood rug delivery and uptake

increased cell ased chemosensitivityased chemosensitivity

mage

induced apoptosis

ModMod

NASOPHANASOPHACARCICARCI

del:del:

ARYNGEALARYNGEAL INOMAINOMA

Out• Intergroup Trial (1998) and

• Chemotherapy Advances fopresent): Induction Concupresent): Induction, Concucombination

• Radiotherapy Advances anpresent)present)

• Role of Biologic Therapy?• Role of Biologic Therapy?

• Biomarker Based Therapy,

lineits application worldwide

or stages II-IVB? (1998-urrent Adjuvant or itsurrent, Adjuvant or its

nd Dose Escalation? (1998-

(2011)(2011)

EBV DNA? (2012 and beyond

INTERGROUP 9Al-Sarraf et a

STRA T & N StageATIF

T & N Stage

P f

AJCC(1992) I

YPerformanceStatus

(1992)I or IV

HistologyI or IVM0M0

99 (RTOG 88-17)al, JCO, 1998

RANDe

RT aloneDOMI

e (70 Gy)

C T hZE

e Conv. Tech

RT (70 Gy) CDDP x 3CDDP x 3

CDDP + 5FU x

NTERGROUP 9Follow Up: 5 years

5 yr progression-free sur

5 yr disease-free survivay

5 ll i l5 yr overall survival

99 (RTOG 88-17) minimum for all pts

( )

CT/RT RTCT/RT RT

rvival 58% 29%(p<0 001)(p<0.001)

al 74% 46%(p<0.001)

67% 37%67% 37%(p<0.001)

INT 0099: Co1 30% WHO t I hi t1. 30% WHO type I histQ: Perhaps chemotherQ: Perhaps chemother

type of histology?

2. RT alone results poo2. RT alone results poocolleagues

Q Old RT t h iQ: Older RT techniquesimprovement of res

ontroversieslology

rapy only benefit thisrapy only benefit this

or when c/w Asianor when c/w Asian

l i i f ths explaining for the ults with chemotherapy

National Cancer CJoseph Wee

AJCC RAND

AJCCDOMI

(1997)ZEIII or IV

M0WHO II/III

N=221

Center-Singaporee, JCO, 2005

RT (70 Gy)Conv Tech.

RT (70 GyRT (70 GyCDDP x 3

CDDP + 5 FU x 3

National Cancer Joseph Wee,

Median F/U:

2 yr Disease Free Surviv2 yr Disease Free Surviv

2 yr distant metastases-f

2 yr overall survival

Center-Singaporet al. JCO, 2005

37.8 monthsCT/RT RT

val 76% 59%val 76% 59%(p=0.027)

free rate 87% 70%(p=0.0007)

84% 77%(p=0.006)

INT 0099: Co3. Compliance to adju

poorp

Q: Alternative chemoth

ontroversiesuvant chemotherapy

herapy combinations?

Neoadjj

CombinCombin

juvant j

nationsnations

hase III Neoadjuvant Che

Neoadjuvant chemothewas no better than RT

N dj t Ch thNeoadjuvant Chemothealone followed by adjuinferior to CCRT followchemotherapy (n=338)chemotherapy. (n=338)

emotherapy Combinations

erapy followed by RT alone. (n=456)

Ma et al. Guangzhou, JCO 2001

f ll d b RTerapy followed by RT vant chemotherapy was

wed by adjuvant ))

Xu et al., Fudan University, Med Oncol 201

NPC: MetCh thChemother

(Langendijk J.A., J

10 Randomized studies10 Randomized studies 4% increase in absolute surv

ith th dditi f h thwith the addition of chemothLARGEST effects with CONC(20% increase in OS)Induction chemotherapy thouInduction chemotherapy thoushow improvement in OSAdjuvant chemotherapy hasAdjuvant chemotherapy has Other Meta-analyses whethe

a-Analysesd RTrapy and RT:

CO 2004;22:4604-4612)

vival at 5 years hherapyCOMITTANT therapy

ugh achieved high RR failed tough achieved high RR failed to

no benefit for OS or RFSno benefit for OS or RFSr showed similar results.

Meta-Analysis Based on

Risk Red ction all chemRisk Reduction all chemRisk Reduction for NeoaRisk Reduction for AdjuvRi k R d i f CRisk Reduction for Conc

Chemotherapy overall cos r i al benefit of 4% atsurvival benefit of 4% at and 6% at 5 years from 5y

n Individual Patient Data

otherap 18%otherapy: 18%adjuvant: 1%jvant: 3%

40%current: 40%

orresponds to an absolute2 ears from 77% to 81%2 years from 77% to 81%

56% to 62%

Baujet et al. IJROBP, 200

Dilemm•Intergroup 0099 and sevet i l t i d dj ttrials contained adjuvant c

•M l h d h•Meta-analyses showed thconcurrent chemoradiothe

•Compliance to adjuvant cp jaround 55%.

•Is there any benefit of thechemotherapy after concurchemotherapy after concurOr does it only add toxicity

ma???eral large Asian randomizedh th ft CCRThemotherapy after CCRT.

h d i f OS b fi ihe driver of OS benefit is erapy.

chemotherapy is low at py

e addition of adjuvant rrent chemoradiotherapy?rrent chemoradiotherapy? y?

NPC Trials suggest CCR

•Lin et al. (n=284) JCO and ReLin et al. (n 284) JCO and Rethan RT alone. Subsequent rCCRT was not seen among hignodal size >6 cm, (2) supracla1992 AJCC stage T4N2, (4) muwith 1 node >4 cm.

••Chan et al. (n=350) JCO andimprovement in OS (p=.06) ani f d f f ilin freedom from failure.

•Kwong et al (n=219) JCO: cKwong et al. (n=219) JCO: cshowed borderline improvem

RT might not be enough

ed Journal. CCRT was bettered Journal. CCRT was better re-analysis showed benefit of igh risk patients defined as (1)g p ( )avicular node metastases, (3) ultiple neck node metastases

JNCI. Showed borderline nd no significant improvement

concurrent chemotherapyconcurrent chemotherapy ent in OS.

NPC Trials suggest CCR

•Exploratory study of NPC9902 (n=187) by Lee et al. sdistant control from concuinadequate.

•It was the adjuvant phasethat showed significant imthat showed significant im

•For the adjuvant phase pFor the adjuvant phase, pmore cycles achieved signFFR than those with 0 1 cyFFR than those with 0-1 cy

RT might not be enough

C-9901 (n=354) and NPC-showed the impact on urrent phase was p

e with the inclusion of 5FUmpact on distant controlmpact on distant control.

patients who received 3 orpatients who received 3 or nificantly better distant-yclesycles.

Sun Yat-Sen GuChen et al., et al, Lan

RAJCC RAND

AJCC(1997) O

MIZ

(1997)III or IV Z

EIII or IV

WExcluded

W

T3-4N0N=508

uanzhou, Chinancet Oncology, 2011

RT (66-75 Gy)( y)Weekly CDDP (40mg/m2)

RT (66-75 Gy)W kl CDDP (40 / 2Weekly CDDP (40mg/m2

CDDP + 5 FU x 3

Median F/U: 37.8 months

Ma et al. Lancet Oncol 2011

Median F/U: 37.8 months

Ma et al. Lancet Oncol 2011

Adjuvant CheAdjuvant Che•Th f il•There were more failurnon-sig in the concurregaround 0.1 in all endpoi

•Around 20% randomizi hnot receive any chemot

•Biggest issue: the trianon-inferiority trial againon-inferiority trial agai

emotherapy?emotherapy?h h i i llres though statistically

nt arm with p value pnts.

zed to adjuvant arm did hherapy.

al was not designed as anst the standardnst the standard.

Synthesis of Adjuvy j

•Major failure with NPC isMajor failure with NPC is

•Hong Kong and Taiwan sHong Kong and Taiwan schemotherapy impacts dis

•Sun Yat Sen trial was notinferiority trial against cur

••It is premature to definitivchemotherapy can be droppy pstandard treatment paradig

vant Chemotherapp

now distant now distant.

studies suggest adjuvantstudies suggest adjuvant stant control.

t designed as a non-rent standard.

vely conclude that adjuvanpped from the current ppgm.

AlternativeAlternative

Can Neoadjuvant A

To Concurrent ChTo Concurrent Ch

To Improve up

To Improve upon paTo Improve upon pa

e Strategy:e Strategy:

Add Further benefit

emoradiotherapyemoradiotherapy

pon DM rates?

atient compliance?atient compliance?

Neoadjuvant followRischin et al. (n=35) [JCO

Phase II trial of inductionPhase II trial of inductionfollowed by CDDP and 60

Induction chemotherapyInduction chemotherapy The estimated 4-year prowas 81% and overall survOnly two patients have haOnly two patients have ha

wed by CCRT trialsO, 2002]

epirubicin CDDP 5 FU epirubicin, CDDP, 5-FU 0Gy.

was well-toleratedwas well-tolerated. ogression-free survival ratevival rate was 90%. ad a locoregional relapse.ad a locoregional relapse.

Neoadjuvant follow

Hong Kong Phase II randocycles of docetaxel and CCDDP vs. weekly CDDP. Ityno compromise in CCRT. hematologic during neoadhematologic during neoadJCO, 2009)H ll i Ph II d iHellenic Phase II randomiCDDP, epirubicin, and pacby concurrent CDDP vs. cdifference in Overall respoendpoints.(Fountzilas et al.

wed by CCRT trials

omized (n=141) used 2 CDDP followed by weekly t was feasible to deliver wi Toxicity was mainly

djuvant phase.(Hui et al.,djuvant phase.(Hui et al.,

d ( 65) 3 l fzed (n=65) 3 cycles of clitaxel q3 weeks followed concurrent CDDP. No onse rates or other Greece, Ann Oncol 2011)

Neoadjuvant follow

NPC-0501GORTECSingapore

These 3 on-going PhaThese 3 on-going Phawhether neoadjuvant cb CCRT i i tby CCRT is superior toIf the trials are positiveIf the trials are positiveparadigm can be one a

wed by CCRT trials

se III trials will addressse III trials will address chemotherapy followed

CCRT lo CCRT alone.e then this treatmente, then this treatment alternative standard.

Can chemothe

benefit

stage III/IVstage III/IV

erapy add any py y

beyond

V patients?V patients?

CCRT vs. RT alonChen et al,

RANDChinese DOMI

Chinese stage

ZEII

N=230edian FU=5 yrs

e for Stage II NPCJNCI, 2011

RT (70 Gy)

RT (70 Gy)( y)Weekly CDDP

(30 / 2)(30mg/m2)

CCRT vs. RT alon

• Chinese stage II whChinese stage II whAJCC II/III patients

• 78% received at leaand 26% received 7and 26% received 7cycles

• No difference in LR

e for Stage II NPC

hich is equivalent tohich is equivalent to

ast 6 cycles of CDDP 7 cycles and 5% 87 cycles and 5% 8

RC (93% vs. 91%)

CCRT vs. RT alon

• 5 year OS: 945 year OS: 94• 5 year PFS: 87• 5 year DMFS: 94

• MVA showed the # of• MVA showed the # ofwas the only indepen

i h b OS PFS Dwith better OS, PFS, D• More acute side effec• More acute side effec

increase in late effect

e for Stage II NPC

.5% vs. 85.8%, p=0.007.5% vs. 85.8%, p 0.007

.9% vs. 77.8%, p=0.17

.8% vs. 83.9%, p=0.007

f chemotherapy cyclesf chemotherapy cycles ndent factor associated Di lDistant controlcts (0=0 001) no sigcts (0=0.001) no sig ts

RadiotherapRadiotherap

Dose and TDose and T

py Advances:py Advances:

TechnologyTechnology

RT Dose E• Altered Fractionation; Br

l t d f ti tiaccelerated fractionation• None of the trials showed

control in the setting of c• Late toxicities observed:• Late toxicities observed:

massive epistaxis, crania

• IAEA randomized trial forIAEA randomized trial forwith induction chemothethose who had a brachytthose who had a brachytany benefit versus those

Escalation?rachytherapy; SRS,

i 2D d IMRTn in 2D and IMRT era.d benefit in terms of tumorchemoradiation.

temporal lobe necrosis temporal lobe necrosis, al neuropathies.

r III-IVB patients treatedr III IVB patients treated erapy followed by CCRT, therapy boost did not havetherapy boost did not have without brachytherapy

Late complicRT fRT for

• Xerostomia• Temporal Lob

O l d d t• Oral and dent• Hearing lossHearing loss • Pituitary hypo• Neural compl

Soft and hard• Soft and hard

cations from NPCr NPC

be Necrosist l li tital complications(more with CCRT)(more with CCRT)ofunctionlicationsd tissue cxd tissue cx

IMRT for N(UCSF, Lee et al, IJ

• N = 87

• PTVg = 70 Gy @ 2.1g y @PTVm = 59.4 Gy @

• T3/T4: 45% III/

• N+: 79%

• Chemotherapy:

NPC: UCSFROBP, 53:1:12-21)

12 Gy concurrently y y1.8 Gy per day

IV: 74%

85%

4 Year Local P

90

100

ate

80

90

Ra

60

70

PF

40

50

cal

20

30

Lo

c

N=8710

20

% L Median F/U=

M3020100

0%Progression-free

97%97%

=30 months

Months70605040

GTV

T3N2 Nasophary

GTV

yngeal Carcinom

Max optic nerves 50 Gy

T3N2

Mean Whole Gland R & Mean Superficial Lobe

Max BS Dose: 50 G

Mean Oral Cavity 40 GMean Oral Cavity 40 G

L Parotid: 30 Gy/29 Gyes only: 23 Gy/22 Gy

IMRT NPC (Sing( gCenter N StageYear

Kwong 33 T1KwongCancer

2004

33 T12004

Kam 63 51%IJROBP, 2004

T3/4

WoldenIJROBP,

74 T1-T4,

2005

gle Institutions)g )F/U Local ControlMo (3-year)24 100%24 100%

29 92% 9 %

35 91%

RTOG PROTIMRT for NPC (Le

RSt I IVb E

GStage: I-IVb

GI

Hi t l59

ST

Histology:WHO I III T

EWHO I-III

R

TOCOL 0225ee N., JCO 2009)

70 Gy to gross disease70 Gy to gross diseaseconcurrently

9.4 Gy to microscopic diseaseOver 33 daysOver 33 days

CT:(≥T2b and/or + LN)

TT--StaStaTT StaSta•• T1:T1:T1:T1:

•• T2a:T2a:

•• T2b:T2b:

•• T3:T3:T3:T3:

T4T4•• T4:T4:

ageageageage24%24%24%24%

18%18%

24%24%

15%15%15%15%

19%19%19%19% Lee et al, JCO, 200

NN--StStNN StStN0N0•• N0:N0:

•• N1:N1:

N2N2•• N2:N2:

•• N3:N3:

tagetagetagetage28%28%28%28%

28%28%

30%30%30%30%

13%13%Lee et al, JCO, 200

Local ProgressiLocal Progressigg

•• 3 year:3 year:

1 l l f il1 l l f il•• 1 local failure 1 local failure

•• 3 local regiona3 local regiona•• 3 local regiona3 local regiona

onon--Free IntervalFree Interval

92.6%92.6%

llonly only

al failuresal failuresal failuresal failuresLee et al, JCO, 200

Regional ProgressRegional Progress

•• 3 year3 year

2 regional failure2 regional failure•• 2 regional failure2 regional failure

•• 5 local and regio5 local and regio•• 5 local and regio5 local and regio

sionsion--Free IntervalFree Interval

90.8%90.8%

es onlyes onlyes onlyes only

nal failuresnal failuresnal failures nal failures Lee et al, JCO, 200

4 Year Distant 100 (UCSF, L

80

60

40

20 N=87

0

0Median F/U=3

302010000

M

Metastases-FreeLee et al, IJROBP, 53:1:12-21)

66%

30 months70605040

Months

4 year Ove90

100 (UCSF,

70

80

90

60

70

40

50

20

30 N=8710

20

Median F/U=33020100

0

M

erall SurvivaLee et al, IJROBP, 53:1:12-21

73%

30 months70605040

Months

IMRT(15 studies)

Local Progress

90-100%90-100%

Distant Met

66% 91%66%-91%

) vs. Conventiona

sion-Free Rate

74%-93%74%-93%

ts-Free Rate

67% 84%67%-84%

RTOG PROTIMRT for NPC (Le

RSt I IVb

7EG

Stage: I-IVbGI

Hi t l59

ST

Histology:WHO I III T

EWHO I-III

R CT

TOCOL 0225ee N. JCO, 2008)

70 Gy to gross diseaseconcurrently

9.4 Gy to microscopidisease

Over 33 days

T:(≥T2b and/or + LN

Local Progressig

•• 3 year:3 year:

1 l l f il1 l l f il•• 1 local failure 1 local failure

•• 3 local regiona3 local regiona•• 3 local regiona3 local regiona

on-Free Interva

92.6%92.6% (34% T3/4

llonly only

al failuresal failuresal failuresal failuresLee et al, JCO, 200

Regional Progressg g

•• 3 year3 year 99

•• 2 regional failures2 regional failures•• 2 regional failures2 regional failures

•• 5 local and region5 local and regiongg

sion-Free Interval

90.8% 90.8% (43% N2/3)

s onlys onlys onlys only

nal failures nal failures Lee et al, JCO, 200

Two randomized tri

NPC showed IMRNPC showed IMR

To Conventional rad

Improving salImproving sal

ials for early-staged

RT to be superiorRT to be superior

diotherapy in terms

ivary functionivary function.

OS and Progressi100100

/ / //

g%

)

75

%)

75

/ /

/ /

viv

al (%

50

viv

al (%

503 year

Su

rv

25

Su

rv

25

3 year

3 year

Overall SurvivalProgression-Free00

ients at Riskients at Risk68

ients at Risk60

ients at Riskients at Risk

Yea0 1

Yea0 1

S6868

6054

ion-Free Surviva

/

RTOG 0225

/

// / / / / // // //// ///////// // // / /////

// / / / / // // //// /////// // // / ///

PFS: 72.7%PFS: 72.7%

0S: 76.5%

e Surviva

47 17

rs after Registration2 3

rs after Registration2 3

4742

1717

Lee et al, JCO, 200

Phase II Study of ConcurUsing 3D CRT or IMRT + B

Regionally Advanced N

RENode + or ≥ T2b EG

Node or ≥ T2b

Histology:WHO I-III

CD

IST 5TE

5

Ree N et al. Lancet Oncol 2011

rrent ChemoradiotherapyBevacizumab for Locally or

Concurrent:

Nasopharyngeal Cancer

Concurrent:

IMRT (70 Gy)

DDP (100mg/m2) x 3 cycles q 3 weeks

Bevacizumab (15mg/kg ) q 3 weekBevacizumab (15mg/kg ) q 3 week

Adj tAdjuvant:CDDP (80 mg/m2)

5FU (1000 / 2) 3 l 3 k5FU (1000 mg/m2) x 3 cycles q3 weeks Bevacizumab ( 15mg/kg ) q3 weeks

2 year DMF and OS rate of ~ 90%

Is there a better m

T and N sT and N s

Selecting the b

For NPCFor NPC

marker other than

staging forstaging for

best treatment

patients?patients?

Biomarker: •Data from Hong Kong (Chan: JNCg g (suggest that post-treatment EBV DN

•Lin et al IJROBP 2007 EBV DNALin et al. IJROBP, 2007 EBV DNA

•EBV DNA clearance has been shotreatment success than PET (Wang

•Wang et al Cancer 117 2011 (n=3Wang et al. Cancer 117, 2011 (n=3recurrences better than PET.

•Could EBV DNA be the reason for different series?

EBV DNAI,JCO) and Taiwan (Lin: NEJM) ) ( )NA is a good prognostic marker.

A most valuable prognostic factorA most valuable prognostic factor.

wn to be a better predictor of pet al. Cancer Research 2010).

5) EBV DNA predicted for all NPC5) EBV DNA predicted for all NPC

differences in outcome among

Biomarker:•Since adjuvant chemotherapyperhaps only select out those pchemotherapy, i.e., those with DNA levels after concurrent ch

•Diff t li i l f l t f•Different clinical useful cut-ofpost-treatment EBV DNA copieDr Quynh Le’s talk during PleDr. Quynh Le’s talk during Ple

•RTOG currently is designingRTOG currently is designing rial. One on-going study at Ho

: EBV DNAy compliance is problematic, patients who need adjuvant persistent detectable EBV emoradiotherapy.

ff h b d dffs have been recommended, es, <500 seem to be the best. enary Session)enary Session)

an EBV DNA directed NPCan EBV DNA directed NPC ong Kong.

NPC: 2012 aSince Intergroup 0099 fro

lti l d i d t i lmultiple randomized trialsadjuvant chemotherapy reStage II patients should bPatients should be offeredPatients should be offeredcoverage and spare normDistant failure is main issMore effective and less toMore effective and less toneeded.P ti t l ti ill b kPatient selection will be k(EBV DNA).

and Beyondm 14 years ago, despite

CCRT f ll d b

ys, CCRT followed by emains the standard.e offered chemotherapyd IMRT to maximize targetd IMRT to maximize target

mal tissues.ue with this disease.

oxic systemic therapy isoxic systemic therapy is

k f ll f t t dikey for all future studies

ORAL CAVITYINCIDENCE OF NOINCIDENCE OF NO

Lip

Fl f M thFloor of Mouth

Oral TongueOral Tongue

Buccal Mucosa

Lower Gingiva

Upper Gingiva &Hard Palate

Retromolar Trigone

Y CARCINOMAODE METASTASESODE METASTASES

5-10%

30%30%

35%35%

9-31%

18-52%

13-24%

40%

ORAL CAVITYINCIDENCE OF

Lip

Fl f M thFloor of Mouth

Oral TongueOral Tongue

Buccal Mucosa

Lower Gingiva

Upper Gingiva &Hard Palate

Retromolar Trigone

Y CARCINOMAOCCULT NODES

5-10%

5 35%5-35%

20-70%20 70%

16%

17-19%

22%

25%

Lymph Nodes in thy p he Head and Neck

Retromolar Trigone Cancer

38 F wi

:declines surgery; hence RT-C, with externg y; ,implant. Did well for 4 yrs. cent recurrence vs new 1o on dorsal tongu

ith painful, ulcerated R tongue massFNA SCCFNA: SCCMRI: T3N1

nal beam as well

e

Treatment and Hea

• Availability of

• CostCost

• I• Insurance

alth-Care Factors

f Expertise

TreatmentTreatment Oral Cavit

Upfront surgiUpfront surgifollowed by y

chemotI th t tIs the treatme

ParadigmParadigmty Cancery

ical resectionical resection radiation +/-therapy

t f h ient of choice

Target VolumeTarget Volume

• Oral Cavity Canc

• Over treatment oOver treatment o

• Survival after Sadefinitive Chemodefinitive Chemo

e Delineatione Delineation

cers

of the N0 neck?of the N0 neck?

alvage for oRToRT

Buccal M

Make sure you have a WIDE m

Risk

Mucosa Cancer

margin to despite T1 lesions

Factor?

Make sure you coMake sure you coover the entire tongueover the entire tongue

Hard Palate Cancer

Adenoidcystic CA with pathM k h thMake sure you chase the n

hology perineural invasiont th B f Sk llnerve to the Base of Skull

MakPlaFOM

SCC of FOM extendin

ke sure that you cover the skin wacement of Bolus in your planni

ng into mandible

… perineural spreadM k V3 i d tMake sure V3 is covered t

35 F with recurrent SCC of gingivo

t th B f Sk llto the Base of Skull

obuccal sulcus. R chin numbness

Old RT: Multiple Junction Points: IMRT has the adThe junction and parotid sparing. Make sure flashThe junction and parotid sparing. Make sure flash

dvantage of smoothingh and Bolus is used.h and Bolus is used.

IMRT can also sIMRT can also sspare the glottic laryspare the glottic lary

Post Op RadiatioPost Op Radiatio

• Any single positive no• More than one positivMore than one positiv• Extracapsular spread

• Primary: Close or + My

P i N k• Primary versus Neck:be comprehensive!

on Therapy(PORT)on Therapy(PORT)

ode >3cmve nodeve noded

Margin, PNI, LVIg , ,

M j it i i t: Majority view is to

Results of EORTC TriaResults of EORTC Tria(POST OP RT vs PO

EORTC 22931(60 mo)

End Point RT RT+CT

p value

T

5 yr DFS 36% 47% .04

5 yr OS 40% 53% .02

Local Control

69% 82% .007

RT t lRT portals were com60-66 Gy and give Chemoth

al 22931 and RTOG 9501al 22931 and RTOG 9501OST OP CHEMO-RT)

RTOG 9501(45.9 mo)

RT RT+CT

p value

T

61% 78% .04

57% 63% .19

72% 82% .01

h i t l !mprehensive portals!erapy for ECE and +Margin

Contralateral LeContralateral Le

Courtesy of Shari Damast

evel 2 Failureevel 2 Failure

Ipsilateral LevIpsilateral Levvel 3 Failurevel 3 Failure

SubmentalSubmentall Failurel Failure

The needThe needcorrecorre

to target to targetectlyectly

Contralateral LeContralateral Leevel 2 Failureevel 2 Failure

Damast et al. Head Neck: Accepted

Ipsilateral LeIpsilateral Leevel 3 Failureevel 3 Failure

Damast et al. Head Neck: Accepte

SubmenSubmenntal Failurental Failure

Damast et al. Head Neck: Accepted

Conclu•

Conclu• As we enter the era of more

need to have a more thoroutarget and patterns of sprea

• There is a need to make surThere is a need to make surprior to planning.

• IMRT should not lead to infeIMRT should not lead to infecompared to conventional t

• f f• In fact results from modern Locoregional results that thfailure to distant metastases

usionusione precision radiotherapy, we ugh knowledge of the tumor ad.re that all cases are scrutinizedre that all cases are scrutinized

erior outcomes whenerior outcomes when techniques.series show superb

here is a changing pattern of s !