LIP AND ORAL CAVITYLIP AND ORAL CAVITYSQUAMOUS CELL SQUAMOUS CELL

CARCINOMASCARCINOMASGuy ANDRY, M.D.Guy ANDRY, M.D.

Dept of SurgeryDept of Surgery

Institut Jules Bordet, U.L.B.Institut Jules Bordet, U.L.B.

Statements 2008 on Head and Neck CancerFrankfurt, 1st & 2nd February 2008

5 Years Survival and Cause Specific 5 Years Survival and Cause Specific Survival %Survival %

LIPLIP ORAL CAVITYORAL CAVITY ∆ ∆

SS CSSCSS SS CSSCSS

St ISt I 7373 8383 6060 6868 1515

St IISt II 6464 7373 4646 5353

St IIISt III 5656 6262 3636 4141 2020

St IVSt IV 4141 4747 2323 2727

After SEER database

LIP LIP CANCERCANCER

The most common primary (~ 25 % of oral The most common primary (~ 25 % of oral cavity cancer)cavity cancer)

~ 12/100.000 habitants per year USA & ~ 12/100.000 habitants per year USA & EuropeEurope

Solar-radiation, tobacco smoking, HPV, Solar-radiation, tobacco smoking, HPV, immunosuppressionimmunosuppression

LIP CANCERLIP CANCERSURGERY IS FIRST SURGERY IS FIRST

CHOICECHOICE

< 2/3 invasion :< 2/3 invasion :–full-thickness pedicled flaps (Abbe or full-thickness pedicled flaps (Abbe or

Estlander)Estlander)

> 2/3 invasion :> 2/3 invasion :–musculo mucosalflaps (Camille Bernard…)musculo mucosalflaps (Camille Bernard…)–free flapsfree flaps–frontal flapfrontal flap

→→ irradiation in debilitated PTSirradiation in debilitated PTS

LIP CANCERLIP CANCERPROGNOSTIC FACTORSPROGNOSTIC FACTORS

Maximum tumor thickness (cf. Martinez-Maximum tumor thickness (cf. Martinez-Gimeno Scoring System)Gimeno Scoring System)

Site (upper & commissure more rapid Site (upper & commissure more rapid growth and preauricular, submandibular growth and preauricular, submandibular lymph node metastases)lymph node metastases)

LIP LIP CANCERCANCER

Scoring system Scoring system → probability of lymph node → probability of lymph node invasioninvasion

Tumor thicknessTumor thickness Martinez-Gimeno Scoring SystemMartinez-Gimeno Scoring System

T stage, T stage, Tumor thicknessTumor thickness, microvascular, perineural invasion, microvascular, perineural invasion

histologic grade of differentiation, presence of inflammatory infiltratehistologic grade of differentiation, presence of inflammatory infiltrate

Group I : Group I : 0 %0 % of of lymph node invasionlymph node invasion

Group II :Group II : 21 %21 %

Group III :Group III : 50 %50 %

Group IV :Group IV : 67 %67 %

LIP CANCERLIP CANCER

Mohs micrographic surgery has been Mohs micrographic surgery has been successfully usedsuccessfully used– No tumor related deaths or metastases at No tumor related deaths or metastases at

5 yrs5 yrs– All PTS with recurrent disease were All PTS with recurrent disease were

successfully salvagedsuccessfully salvaged

LIP CANCERLIP CANCERTT11 T T22

SurgerySurgery ifif + margins+ margins+ lymph nodes+ lymph nodes

Adjuvant radiationAdjuvant radiationRadiationRadiation if recurrence local regionalif recurrence local regional

External beamExternal beamBrachytherapyBrachytherapy Salvage surgerySalvage surgeryor bothor both

98 % local control 5 yrs98 % local control 5 yrs

LIP CANCERLIP CANCER

There are no published randomized trials There are no published randomized trials onon• the use of sequential surgery + radiation the use of sequential surgery + radiation • the use of chemotherapythe use of chemotherapy

NBNB : one preliminary study on super selective : one preliminary study on super selective intraarterial chemo (CDDP based) in six PTS with intraarterial chemo (CDDP based) in six PTS with TT11, T, T22 or local recurrence by Kishi & al, Radiology or local recurrence by Kishi & al, Radiology

213, 1999213, 1999

FLOOR OF MOUTH FLOOR OF MOUTH CANCERCANCER

High risk tumors (even in early stages)High risk tumors (even in early stages) Proximity to the mandibleProximity to the mandible

– Adhesion or invasion (by the alveolar ridge)Adhesion or invasion (by the alveolar ridge)– Risk of radiation induced bone necrosisRisk of radiation induced bone necrosis

No mechanical barrier in soft tissuesNo mechanical barrier in soft tissues– Blurred vision of margins, Even with high resolution MRIBlurred vision of margins, Even with high resolution MRI

Early lymph node metastasesEarly lymph node metastases– 20 % of occult invasion in T20 % of occult invasion in T11

– 62 % of occult invasion in T62 % of occult invasion in T22

Will develop second primary tumors (Will develop second primary tumors (~ 20 % in T~ 20 % in T11 – – TT22) ) “field cancerization” effect of carcinogens“field cancerization” effect of carcinogens

FLOOR OF MOUTH FLOOR OF MOUTH CANCERCANCER

Surgery is generally preferred for TSurgery is generally preferred for T11 T T22 (primary & necks)(primary & necks)

+ radiation+ radiation if margins are close or involvedif margins are close or involved

if lymph nodes are involved if lymph nodes are involved (CR)(CR)

if mandible is invadedif mandible is invaded

if perineural or/and vascular if perineural or/and vascular invasion invasion

(or chemo radiation)(or chemo radiation) Role of sentinel node biopsy is under studyRole of sentinel node biopsy is under study

FLOOR OF MOUTH FLOOR OF MOUTH CANCERCANCER

Surgery S 5 yrsSurgery S 5 yrs

TT11 95 %95 %

TT22 86 %86 %

Control rateControl rate

90 %90 % ← ← negative negative marginsmargins

62 %62 % ← ← positive positive marginsmargins

Primary ERTPrimary ERT

Control rateControl rate

90 %90 % TT11

77 %77 % TT22

Neck surgery when invasion depth ≥ 5 mm

level I to III unilateral for lateral tumors

bilateral for anterior/midline

ORAL TONGUE CANCERORAL TONGUE CANCERTT11 T T22

SURGERYSURGERY Partial glossectomy (negative margins Partial glossectomy (negative margins > 1 > 1

cm)cm)

→ → thickness, depth invasion, perineural spread, thickness, depth invasion, perineural spread, vascular invasionvascular invasion

Elective neck node dissectionElective neck node dissection-- TT11 TT22 T T33 T T44 N N00

NN++ 6 % 6 % 36 %36 % 50 %50 % 67 %67 %

Staging is crucial in defining the postsurgical treatment ERT + CHEMO

After Hickx WL. & al, Am J Otolaryngol 1998

ORAL TONGUE ORAL TONGUE CANCERCANCER

Role of elective neck dissection for T1 N0 ?No randomized Trial

Retrospective studies remain controversialTT1-21-2 N N00 ELNELN TNDTND

Yii (RoyalMarsden)Yii (RoyalMarsden) RECREC 7777 27 %27 % 50 % 50 % (p.025)(p.025)

19991999 S S 5yrs5yrs 75 %75 % 65 % (NS)65 % (NS)

ELNELN TNDTND

Haddadin Haddadin (Canniesburn)(Canniesburn)

19981998S S 5yrs5yrs 137137 81 %81 % 45 % 45 %

(p.001)(p.001)

But bias in the initial treatments (various types of surgery, RT or no RTto the primary and/or to the neck)

ELECTIVE VERSUS THERAPEUTIC NECK ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERSDISSECTION IN ORAL CAVITY CANCERS

Randomized trialRandomized trial

39 ELND39 ELND 36 36 observationsobservations

TT1-3 1-3 NN00 49 % N49 % N+ + 47 % N47 % N+ + : TND: TND

13 % CR13 % CR 25 % CR25 % CR

DFS DFS 5 yrs5 yrs 57 % 57 % 60 % NS60 % NS

NB : NB : 16 % of second primaries16 % of second primaries45 % of deaths met caused by the original tumor45 % of deaths met caused by the original tumorAfter Vandenbrouck & al, Cancer 46 ; 1980

ELECTIVE VERSUS THERAPEUTIC NECK ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERSDISSECTION IN ORAL CAVITY CANCERS

Randomized trialRandomized trial

30 hemiglossectomy + RND30 hemiglossectomy + RND 40 hemiglossectomy40 hemiglossectomy

10 N +10 N + 20 N-20 N- 23 N+ 23 N+

↓↓4 contralat +4 contralat +

47 % N+47 % N+ 57 % N+57 % N+

DFSDFS 63 %63 % N.SN.S 52 %52 %

(T(T11 : 70 % ; T : 70 % ; T2 2 : 60 %): 60 %) (T(T11 : 64 % ; T : 64 % ; T22 : : 46 %)46 %)

After Fakih & al, Am. J. Surg. 158; 1989

ELECTIVE VERSUS THERAPEUTIC NECK ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERSDISSECTION IN ORAL CAVITY CANCERS

Randomized trialRandomized trial : effect of tumor depth in 51 PTS : effect of tumor depth in 51 PTS

21 Hemiglossectomy + ELN21 Hemiglossectomy + ELN 30 30 hemiglossectomyhemiglossectomy

9 (≥ 4 mm)9 (≥ 4 mm) 12 ( 12 (< 4 mm)< 4 mm) ↓↓ ↓↓

6 N6 N++ (67 %) (67 %) 1 N1 N++ (8 %) (8 %)

S 43 % (p < 0.01)S 43 % (p < 0.01)S 81 %

After Fakih & al, Am. J. Surg. 158; 1989

21 (≥ 4 mm)21 (≥ 4 mm) 9 (9 (< 4 mm)< 4 mm)

↓↓ ↓↓

15 N+ (76 %)15 N+ (76 %)2 N+ (22 %)2 N+ (22 %)

LOWER ALVEOLAR RIDGE & LOWER ALVEOLAR RIDGE & RETROMOLAR TRIGONE TRETROMOLAR TRIGONE T1-21-2 cancers cancers

SURGERYSURGERY Wide local excision with marginal Wide local excision with marginal mandibulectomymandibulectomy

- close proximity to bone- close proximity to bone

- infiltration into the masticator space- infiltration into the masticator space

- nodal involvement- nodal involvement

RADIATIONRADIATION AdjuvantAdjuvant for close or positive marginsfor close or positive margins

for lymph node invasionfor lymph node invasion

OR if used as first modalityOR if used as first modality

UPPER ALVEOLAR RIDGE & HARD UPPER ALVEOLAR RIDGE & HARD PALATE CANCERSPALATE CANCERS

SURGERYSURGERYResection of part of the palatine processResection of part of the palatine process→ → maxillectomy followed by flapmaxillectomy followed by flap

reconstruction or prosthetic rehabilitationreconstruction or prosthetic rehabilitation-- St I St I (9)(9) St II St II (19)(19) St III St III (14) (14) St IVSt IV(20) *(20) *

CSSCSS 75 % 75 % 46 %46 % 36 %36 % 11 %11 %

- neck dissection in Stage III- neck dissection in Stage III RADIATIONRADIATION : alone or used for close margins, bulky & : alone or used for close margins, bulky &

infiltrating tumors, nodal spreadinfiltrating tumors, nodal spread

After Evans & Shah, Am J Surg 1981

BUCCAL MUCOSA CANCERSBUCCAL MUCOSA CANCERS SURGERYSURGERY

transoral resection transoral resection ++ check flaps check flaps++ mandibular resection mandibular resection++ maxillectomy maxillectomy- Neck : advocated for T- Neck : advocated for T22 or invasion > 5 mm, muscle or invasion > 5 mm, muscle

St I St I St II St II St IIISt III St IVSt IV

**

78 % 78 % 66 %66 % 62 %62 % 50 %50 %

NN00 necks : 70 % → rec rate if no END or RT : 25 % vs 10 % (p<.05) necks : 70 % → rec rate if no END or RT : 25 % vs 10 % (p<.05)

NN++ necks : 49 % (no CR : 69 % vs +CR : 24 %) necks : 49 % (no CR : 69 % vs +CR : 24 %)After Diaz & al, Head & Neck 2003

+ free flaps

S 5yrsS 5yrs

S 5yrsS 5yrs

BUCCAL MUCOSA CANCERS BUCCAL MUCOSA CANCERS (2)(2)

RADIATIONRADIATION : :

Used primarily for cure of T Used primarily for cure of T 1-21-2

→ → S3yrs : St I = 85 % ; St II = 63 %S3yrs : St I = 85 % ; St II = 63 % * *

Postop advocated for high riskPostop advocated for high risk

-- margins < 2 mmmargins < 2 mm- perineural invasionperineural invasion- lymph node involvementlymph node involvement

After Nair & al, Cancer, 1988

CONCLUSIONS (1)CONCLUSIONS (1)

Prognostic factors in oral cavity SCCAPrognostic factors in oral cavity SCCA T size remains an «old timer»T size remains an «old timer» Depth of invasion is more informativeDepth of invasion is more informative

– as areas are perineural spreadperineural spread

vascular invasionvascular invasion N involvement is a state of emergency N involvement is a state of emergency

from prompt an multidisciplinary from prompt an multidisciplinary aggressive treatmentaggressive treatment

CONCLUSIONS (2)CONCLUSIONS (2)

No neck should not be a cause of debate No neck should not be a cause of debate on what is to be done in a randomized trialon what is to be done in a randomized trial

Depth of invasion of the primaryDepth of invasion of the primary Status of margins (close, involved, Status of margins (close, involved,

dysplasia,… molecular markers)dysplasia,… molecular markers) Perineural spreadPerineural spread Vascular invasionVascular invasion

– ShouldShould be routinely reported andbe routinely reported and

be the basis of planned treatmentbe the basis of planned treatment