Recurrence patterns in squamous cell carcinoma of the oral cavity, pharynx, and larynx

Recurrence Patterns in Squamous Cell Carcinoma of the Oral Cavity, Pharynx, and Larynx ................................................................................. ................................................................................. HARVEY GILBERT, M.D., and A. ROBERT KAGAN, M.D.

The purpose of this review is t o document patterns of failure with the existing modalities of therapy in carcinomas of the upper aerodigestive tract. Most attention is given to regional failure, which is separately divided into primary site and metastatic cervical adenopathy. Survival, stage of the lesion, conversion of the clinically negative neck, and salvage of treatment failure is discussed.

remains in the primary site.

failures (16%).

failure rate seen not only in the neck but also in the primary site with or without distant metastases. Nodal involvement indicates mostly the aggressive biological nature of the primary lesion. The most common failing by authors, whose reports had t o be excluded from this review, was a preoccupation with survival statistics and a general inattention paid t o documenting the specific failure site.

Either with surgery, radiations or combination, the commonest regional failure still

Of additional importance is the unexpectedly poor salvage rate of previous treatment

Histologically involved lymph nodes appears to portend a poor prognosis with a high

................................................................................. .................................................................................

INTRODUCTION

Surgeons and therapeutic radiologists agree that squamous cell carcinoma of the oral cavity, oropharynx, and laryngopharynx can be treated in various ways. The improvements in radiotherapeutic skills have encouraged surgeons to suggest to their patients that they might fare better with irradiated tissues than with the physiologic or cosmetic deficit that incurs from surgery. There is little doubt that

From the Departments of Radiotherapy, Southern California Permanent Medical Group and Kaiser Foundation Hospital, 1510 No. Edgemont Street, Los Angeles, California 90027.

H. Gilbert was formerly from UCLA Medical Center, Department of Radiation Therapy, Los Angeles, California

Journal of Surgical Oncology 0 1974 Alan R. Liss, Inc., 150 Fifth Avenue, New York, N.Y. 10011 357

358 Gilbert and Kagan

preservation of the mandible, maintenance of mastication, deglutition, the ability to talk, and normal shoulder and head movements can often be compatible with curative irradiation.

In centers where radiation therapy is dominant, the majority of these tumors are given a therapeutic trial of radiations 3.500-5000 rads in 3% to 6 weeks, and if no response is obtained, the patient is referred for surgery. Further- more, the irresponsible, smoking, alcoholic patient is treated by surgery. These practices leave the therapeutic radiologist with a group of patients whose survival has prognostic advantage. Chardot (1972) reported on 21 1 male patients with T,-T3 lesions treated mainly by combined treatment. He investigated the in- fluence of staging, smoking, ethanol intake, and weight loss during therapy on survival and regional recurrence. He clearly showed that weight loss, alcohol, and tobacco were as important prognostic factors as anatomic site, extension, and lymph nodal metastases. Kolson (1 970) showed that only one-half of patients with carcinomas of the intrinsic and extrinsic larynx died with residual disease; the others in this series died of distant disease and other causes.

A review of the literature has revealed to us that most patients are treated on the basis of scientific assumption and opinion since the clinician is guided by his experience which is based on a select group of patients.

As therapeutic radiologists we are prejudiced to the concept of treating the patient with radiations and salvaging the failures with surgery. However, at best, only one-half of the radiation failures at the time of diagnosis of failure are operable and only one-half of these can be cured with appreciable post- operative morbidity. It is therefore important to try to determine the effective- ness of radiation in these diseases. The virtues of radiation therapy are con- stantly being expounded, but our purpose here is an attempt to clarify the probability of failure so that a proper perspective can be ascertained. It is important to refrain from radiation therapy if the end result will be harmful t o the patient.

The purpose of this paper is t o discuss local and lymph nodal recurrences with respect to radiations so that proper emphasis can be given to reduction in deformity and maintenance of function in treatment planning for these carcinomas.

METHODS

A selective review of the literature was undertaken to accumulate statistics which have universal value. Many clinicians neglected to describe extent of tumors, selection of cases, and treatment policies in such a manner as to be easily charted. Most often, survival rates were given without a detailed report of how failure occurred.

have defined three main categories: Staging systems are not identical. In order to circumvent this problem we

359 Recurrences in Head and Neck Cancer

1) early and later tumors being TIzZ and T3.4, respectively, 2) the clinically negative neck, No, and 3) early and late lymph nodal involvement being N1 and N2-3, respectively.

With respect t o these three categories, we recognize that it is the policy of some clinicians to palliate or include large primary lesions on investigative trials, thereby excluding them from analysis. Furthermore, fixation or the presence of clinically positive lymph nodes in the neck is an observation, not a scientific fact. Neither the level of nodal involvement nor the number of nodes in the neck affects our three categories.

must be emphasized that many factors affect patient survival and therefore emphasis will be placed on regional disease failure. Failures in distant sites, inter- current disease, operative mortality, and second cancers are major problems but are not dealt with in the tables. A failure in the primary site and in lymph nodes will be denoted as a failure at the primary site. Thus failures will be charted in two categories: 1) failure at the primary site, and 2) failure in the neck.

Survival rates will be given so that comparisons can be made. However, it

RESULTS

Tables I-XI1 form the data for this review. The major problem we en- countered was a diminution from the total number of patients to form a “determinate” group for analysis. In order t o make comparisons, representative information must be obtained. We have used estimates whenever necessary and feel that the trends presented are accurate.

The format to be followed in our tables is as follows:

Column 1 is the number of patients evaluated; Column 2 is the percentage of these cases with advanced primaries (T3 - T4).

Column 3 is the number with No (clinically negative) necks; Column 4 represents the number of originally No necks that became

Column 5 represents the number of clinically positive nodes on admission; Column 6 lists the percent of Column 5 thar are N, or N3 by the UICC

staging system; Column 7 represents the regional failures with the numerator indicating

the number of primary alone and primary plus other failures, and the denominator giving the neck only failures;

Column 8 lists the percent of total regional failures (sum of numerator and denominator in Column 7) that failed in the primary site (numerator of

Column 7). This is the percent of failures, not the percent of all patients;

UICC or AJC);

positive at a later date;


Column 9 lists the appropriate survival figures which in most cases was the

Exact mathematics was extremely difficult to achieve because of the problem of shifting denominators in the literathre. As close an approximation as possible was made with the facts supplied.

absolute 5-year survival.

DISCUSSION OF TABLES I-XI1

Table I. Recurrence Patterns in Carcinomas - Multiple Sites of Origin

Table I lists the recurrence patterns in carcinomas of multiple sites. The survivals in the surgery and irradiation series are similar and differences depend largely on the percent of advanced primaries and/or advanced cervical adenopathy. The percent recurrence of the primary with or without neck recurrence seems to be higher with any form of treatment.

Advanced cervical adenopathy may be controlled by irradiation (Votava et al., 1972; Wizenberg et al., 1972). However, what is more significant is that the primary, in cases with advanced cervical adenopathy, is likely to be un- controlled. Only 10-20% of these cases relapse in the neck done (Jesse and Fletcher, 1963). The association of significant primary failure with conversions (Fayos and Lampe, 1972) and negative necks has also been noted in patients whose first echelons of nodes was treated as part of treating the primary. If the neck recurrence occurs one year after treatment of the primary, the survival appears better than an earlier recurrence (Mustard and Rosen, 1963). Contralateral neck recurrence (Farr and Arthur, 1972;Yonemoto et al., 1972) can be an important cause of failure in a surgical series. Local recurrence in oropharyngeal carcinoma is higher when compared to oral cavity (Farr and Arthur, 1972). Farr reported local failures ranging from 45% in oral cavity to 50-60% in oropharynx. Of 300 No cases, he reported neck only failure in 33 and again showed that the neck is infrequently the major problem.

positive lymph nodes metastases in most series. The incidence of distant metastases is related to the presence of histologically

Table 11. Patterns of Recurrence in Epidermoid Carcinoma of the Anterior 213 Tongue

of advanced primaries and/or cervical adenopathy. The predominence of neck only recurrences in the irradiation series by Pierquin (1971) and the surgical series of Spiro (1971)is because the neck nodes, if clinically negative, were left untreated. In general, however, neck failure appeared to be associated with primary failure.

The differences in survival can not be explained entirely by the percentage

Tab

le I.

Rec

urre

nce P

atte

rns i

n C

arci

nom

as - M

ultip

le S

ites o

f Ori

gin

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Site

s Pa

tient

s Pr

imar

ies

Nod

es

Nod

es

Nod

es

Nod

es

Nod

e A

lone

R

ecur

renc

e S

Yea

r

Fayo

s (1

972)

M

usta

rda

(196

3)

Lede

rman

(1

967)

St

rong

(1

966)

Wiz

enbe

rg

(197

2)

Vot

ava

(197

2)

Surg

ery

Farr

(1

972)

Yon

emot

o (1

972)

St

rong

C

(196

6)

Cha

rdot

d (1

972)

Ben

ak

(197

0)

Ora

l cav

ity

206

3s

206

43

0 0

5314

93

55

To

nsil

Ora

l cav

ity

290

42.5

0

0 29

0 31

11

7/46

72

32

Oro

phar

ynx

456

N.A

. 14

9 N

.A.

307

N.A

. N

.A.

N.A

. 16

Ora

l cav

ity

164

N.A

. 64

N

.A.

100

N.A

. 34

/S5b

N

.A.

N.A

. O

roph

aryn

x L

aryn

goph

aryn

x O

ral c

avity

10

9 N

.A.

0 N

.A.

109

87

38/1

1 77

.5

26

Or o

phar

ynx

Lar

yngo

phar

ynx

Ora

l cav

ity

75

76

0 N

.A.

75

100

3011

s 67

27

O

roph

aryn

x

path

Ora

l cav

ity

946

40

490

N.A

. 45

6 N

.A.

4021

115

78

42

Oro

phar

ynx

Lary

ngop

hary

nx

Ora

l cav

ity

106

N.A

. 58

N

.A.

48

N.A

. 44

17

82

23

Ora

l cav

ity

111

N.A

. 28

N

.A.

83

N.A

. 20

125

44

N.A

. O

roph

aryn

x La

ryng

opha

rynx

Oro

p har

ynx

Lar y

ngop

hary

nx

Ora

l cav

ity

21 1

N

.A.

96

N.A

. 11

5 N

.A.

41/2

5 62

33

Ora

l cav

ity

173

27

173

N.A

. N

.A.

N.A

. N

.A.

N.A

. 5

3

~~

aPri

mar

y tr

eate

d by

x-r

ay a

nd n

eck

by s

urge

ry in

CIn

clud

es ir

radi

atio

n ca

ses.

24

2 =

surg

ery

only

in 4

8.

~

bInc

lude

s no

des

alon

e an

d no

des

plus

pri

mar

y.

dInc

lude

s ra

diat

ion

com

bine

d w

ith

surg

ery.

N

.A.

= N

ot a

vaila

ble.

Tabl

e 11

. Pa

tter

ns o

f R

ecur

renc

e in

Epi

derm

oid

Car

cino

ma

of th

e A

nter

ior

213

Ton

gue

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

%

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

Prim

ary

Surv

ival

N

o.

Adv

ance

d L

ymph

of

Nec

k Po

sitiv

e L

ymph

L

ymph

R

ecur

renc

e 5

Yea

r R

adia

tion

Pati

ents

Pr

imar

ies

Nod

es

Nod

es

Nod

es

Nod

es

Nod

e A

lone

Flet

cher

(196

2)

41

78.

N.A

. N

.A.

N.A

. N

h.

6lN

.A.

N.A

. 51

B

reed

(19

68)

139

48

63

N.A

. 76

58

70

lN.A

. N

.A.

N.A

.

-

Ric

hard

(19

71)

Fayo

s (1

969)

Sa

xena

(19

70)

Kuh

n (1

970)

M

usta

rd (1

963)

Pi

erqu

in (1

971)

Su

rger

y Sp

iro

(197

1)

Tule

nko

(196

6)

Cre

wsb

(19

71)

Flet

cher

(196

2)

162

56

I8

NA

84

45

72

/21

77

18

~ .-

_.

. ....

80

63

76

N.A

. 4

25

2ii

8

70

51

419

69

N.A.

N

.A.

N.A

. N

.A.

274l

N.A

. N

.A.

31

N.A

. N

.A.

262

32

I26

N.A

. 13

6 73

46

4 N

.A.

176

147

288

N.A

. N

.A.

N.A

. 34

24

5 43

13

4 67

11

1 41

75

/70

52

46a

1 2 1

/N. A

.

145

7 14

5 90

64

38

22

5 N

.A.

N.A

.

60

0 0

45/2

5 50

62

N

.A.

N.A

. N

.A.

2011

1

64

36

N.A

. N

.A.

N.A

. 77

/N.A

. N.

A.

N.A

. 8

50

N.A

. N

.A.

N.A

. N

.A.

61N

.A.

N.A

. N

.A.

aThr

ee-y

ear

surv

ival

. bh

clud

es ra

diat

ion

com

bine

d w

ith

surg

ery.

Tabl

e 11

1. Pa

tter

ns o

f R

ecur

renc

e in

Eoi

derm

oid

Car

cino

ma

of t

he B

ucca

l Muc

osa

Rad

iatio

n

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

lval

Pa

tien

ts

Prim

arie

s N

odes

N

odes

N

odes

N

odes

N

ode

Alo

ne

Rec

urre

nce

5 Y

ear

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

70

%

Flet

cher

(19

62)

21

66

N.A

. N

.A.

N.A

. N

.A.

O/N

.A.

0 56

B

reed

(19

68)

46

30

28

N.A

. 18

50

17

lN.A

. N

.A.

N.A

. K

rish

nam

urth

i (19

71)

927

90

260

N.A

. 66

7 21

52

8 M

ajor

ity

34

Mus

tard

(19

63)

237

N.A

. 14

5 38

92

N

.A.

N.A

. N

.A.

49

Surg

ery

Cre

wsa

(19

71)

85

N.A

. N

.A.

aInc

lude

s ra

diat

ion

com

bine

d w

ith

surg

ery.

N.A

. N

.A.

N.A

. 21

lN.A

. N

.A.

N.A

.


The primary control rate with T4 lesions of tongue by irradiation is very poor (F'ierquin et al., 1971 ; Saxena, 1970). The failure rate in T I lesions with surgical salvage varies from 6% (Fletcher and Jesse, 1962) to 18% (Fayos and Lampe, 1969), to 28% (Saxena, 1970). The high failure rate for late lesions is also valid for surgery (Spiro and Strong, 1971). Although the size of the lesion is important, involvement by the primary of certain anatomic sites worsens survival: base of tongue and floor of mouth (Tulenko et al., 1966).

survival and positive adenopathy is not necessarily related to the presence of an advanced primary. In early lesions, Pierquin (1971) showed a 72% 3-year survival in the negative neck but 47% 3-year survival in predominantly early nodes. Strong (1971) confirms this. However, clinical assessment of node involvement is well known to be inaccurate. The importance of truly positive adenopathy is demonstrated by Tulenko (1 966), who showed that pathologically negative node patients had a 5-year survival of 77% whereas histologically positive node patients had an 1 1 % survival.

The majority of patients who failed in the neck alone had early tongue lesions when compared to patients who failed both in the neck and primary site.

The presence or absence of clinically involved lymph nodes also affects

Table 111. Patterns of Recurrence in Epidermoid Carcinoma of the Buccal Mucosa

The rarity of carcinoma of the buccal mucosa makes any conclusions difficult. Further difficulty is magnified by the lack of pertinent statistical data, which is epidemic in this literature. Articles giving survival rates on the basis of treatment with little concern for anatomic site of failure or proper staging had t o be rejected.

Pertinent data are seriously needed before scientific conclusions can be drawn.

Table IV. Patterns of Recurrence in Epidermoid Carcinoma of the Floor of the Mouth

The lack of data concerning nodal failures emphasizes the serious concern of the physician with the primary. Even moderate surgery in this region can be functionally morbid. The patients with nodal disease fail regionally (primary site and nodes) and rarely in the primary site or nodal site alone. This failure pattern also occurs in conversion patients and thus emphasizes the fact that the primary is often large and aggressive in patients who convert or have positive necks at presentation (Harrold, 1971). Seventy percent of Correa's (1 967) failures were in the positive nodal group and this study indirectly discourages the irradiation of positive nodes by emphasizing the aggressive primary lesion which occurs with positive adenopathy. Campos (1 97 1) emphasizes another point of view, stating that in the negative nodal patients, the size of the primary does not

Tabl

e Iv

. Pa

tter

ns O

f R

ecur

renc

e in

Epid

erm

oid

Car

cino

ma af t

he F

loor

of

the

Mou

th

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Pa

tient

s Pr

imar

ies

Nod

es

Nod

es

Nod

es

Nod

es

Nod

e A

lone

R

ecur

renc

e 5

Yea

r

Bre

ed (

1968

) 43

32

C

orre

a (1

967)

15

2 50

C

ampo

s (1

971)

89

25

M

usta

rd (

1963

) 12

8 N

.A.

Surg

ery

Alf

ord

(195

8)

Flet

cher

(196

2)

Har

rold

(19

71)

29

0 28

40

16

3 38

21

56

63

52

24

N.A

. 44

8

N.A

. 22

12

18

/N.A

. N

.A.

N.A

. N

.A.

96

52

N.A

. N

.A.

28

13

26

50

N.A

. N

.A.

34

34

76

N.A

. N.A.

N.A

. 42

4 5

0 2/

N.A

. N

.A.

65

N.A

. N

.A.

N.A

. 1/

N.A

. N

.A.

67

137

31 5

22

510

N.A

. 36

~~

~

~~~

aInc

lude

s rad

iati

on c

ombi

ned

wit

h su

rger

y.

Tabl

e V.

Pa

tter

ns o

f R

ecur

renc

e in

Epi

derm

oid

Car

cino

ma

of t

he L

ower

Gin

giva

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Pati

ents

Pr

imar

ies

Nod

es

Nod

es

Nod

es

Nod

es

Nod

e A

lone

R

ecur

renc

e 5

Yea

r

Flet

cher

(196

2)

Mus

tard

(196

3)

Surg

ery

Cad

y (1

969)

C

rew

sa (

1971

)

14

12

N.A

. N

.A.

N.A

. N

.A.

3/N

.A.

N.A

. 68

26

3 N

.A.

131

50

132

N.A

. N

.A.

N.A

. 35

320

N.A

. 18

2 N

.A.

138

N.A

. 85

M

ajor

ity

36

42

N.A

. N

.A.

N.A

. N

.A.

N.A

. 19

/N.A

. N

.A.

N.A

.

aInc

lude

s rad

iati

on c

ombi

ned

with

sur

gery

.


affect survival. Harrold (1971) refutes this; in his patients size of primary did affect survival in negative necks. Clinically negative necks had a 72% 5-year survival. In contrast N1 nodes showed a 31% 5-year survival, thus emphasizing the importance of even early adenopathy on survival.

Table V. Patterns of Recurrence in Epidermoid Carcinoma of the Lower Gingiva

The high 5-year survival in the irradiation series of Fletcher (1962) reflects the treatment policy of using combined treatment in the late lesions and being able to salvage radiation failures early because lower gingival lesions can easily be followed. In Cady’s surgical series (1969) it should be emphasized that cervical adenopathy more extensive than level I has a poor prognosis. Advanced lesions and level I1 adenopathy are often associated and yield rare cures (Cady and Catlin, 1969). In Cady’s series surgical failures cannot be explained by procedures less extensive than a subtotal mandibectomy.

Again the failure to document sites of failure and reasons for death make an in-depth analysis of this lesion impossible.

Table VI. Patterns of Recurrence in Epidermoid Carcinoma of the Tonsillar Region

The classification of these tumors regardless of attempts of staging is difficult because usually more than one anatomic site is involved.

Survival varies from 20-70%, with the more advanced lesions having the poorer survival figure. Good survival with over 50% advanced lesions has been reported (Fletcher and Lindberg, 1966; Perez et al., 1972). Perez (1972) states that N, survival is 40%, with bilateral adenopathy yielding infrequent survivors.

The pattern of primary to nodal recurrence ranges from 10: 1 in a relatively early series (Wang, 1972) to 1 :1 in a similar early series (Fayos and Lampe, 1971). Local control of these lesions varies with T size (Fayos and Lampe, 1971), with T1 - T2 lesions failing in 28% and T3 - T4 lesions failing in 70% of cases. Perez (1972) shows a higher failure rate in T2 of 35%. In general, the primary fails at least twice as often as the nodes in the neck. Unlike carcinomas of the floor of the mouth and gingiva, where neck adenopathy is usually associated with an advanced primary lesion, positive nodes can be present with a moderate size primary in the tonsillar region. We feel this indicates a biologic aggressive primary rather than mere anatomic extension. Furthermore, and of equal importance, advanced adenopathy appears commonly with tonsillar region carcinoma and can be controlled more effectively with irradiation therapy than adenopathy from most other sites (Jesse and Fletcher, 1963).

Size of tumor is important, however, and we and others feel that involvement of adjacent structures, especially base of tongue, is a critical prognosticator for failure (Rider, 1962). This site of failure is not stressed by Perez (1972). In

Pere

z (1

972)

Ton

sil f

ossa

W

ang

(197

2) T

onsi

l reg

ion

Fayo

s(l9

71)

Tons

il re

gion

C

Jess

e (1

963)

All

orop

hary

nx

Rid

er (1

962)

Ton

sil r

egio

n En

nuye

re

Soft

pal

ate

(195

6)

Flet

cher

A

nter

ior

(196

2)

Tons

illar

Pi

llar

Flet

cher

To

nsil

(196

2)

Flet

cher

So

ft p

alat

e (1

962)

Fl

etch

er

Ret

rom

olar

(1

966)

Tr

igon

e Fl

etch

er

Tons

illar

(1

966)

Fo

ssa

Flet

cher

So

ft p

alat

e (1

966)

67

129

102

267

232

121

47

48

18

129 89

44

61

41

43

50

56

N.A

.

N.A

.

N.A

.

42

62

46

Tabl

e V

I. Pa

tter

ns o

f R

ecur

renc

e in

Epi

derm

oid

Car

cino

ma

of t

he T

onsi

llar R

egio

n

No.

N

O.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Si

tes

Pati

ents

Pr

imar

ies

Nod

es

Nod

es

Nod

es

Nod

es

Nod

e A

lone

R

ecur

renc

e 5

Yea

r -

25

N.A

. 42

55

32

/18J

N

.A.

40a

129

N.A

. 10

0 33

11

8/14

88

38

b 48

N

.A.

54

41

42/4

0d

N.A

. 40

10

9 N

.A.

158

70

62/1

6 80

42

11

6 N

.A.

116

N.A

. 16

5133

83

20

64

lN.A

. N

. A.

17

N.A

. N

.A.

N.A

. N

.A.

712

78

40

N.A

. N

.A.

N.A

. N

.A.

815

60

42

N.A

. N

.A.

N.A

. N

.A.

012

N.A

. 76

65

4 64

62

12

15

71

69f

22

N.A

. 67

72

15

18

65

42

23

1 21

47

81

5 64

64

TABL

E VI (C

ontin

ued)

Surg

ery

Pere

z’

Tons

il fo

ssa

59

49

22

N.A

. 31

43

24

1215

N

.A.

50

Ten

h To

nsil

foss

a 32

0 N

.A.

N.A

. N

.A.

N.A

. N

.A.

1631

64

72

20

(196

7)

(197

2)

aTon

silla

r reg

ion

incl

udes

ant

erio

r ton

silla

r pill

ar, r

etro

mol

ar tu

gone

and

tons

illar

fos

sa.

b3-y

ear

surv

ival

. %

elud

es so

ft p

alat

e an

d gl

oss0

pal

atin

e su

lcus

. dT

en p

atie

nts

prim

arie

s and

9 n

ecks

who

se lo

cal a

nd re

gion

al d

isea

se st

atus

was

unk

now

n ar

e in

clud

ed in

the

recu

rren

ces,

Per

cent

pri

mar

y re

curr

ence

eQuo

ted

from

Mos

s and

Bra

nd, i

n “T

hera

peut

ic R

adio

logy

,” 1

969.

f2

-yea

r sur

viva

l. gN

eck

alon

e fa

ilure

was

not

giv

en.

hSur

gery

and

com

bine

d.

!Sur

gery

or i

rrad

iatio

n.

]Nod

es a

re n

ot n

odes

alo

ne b

ut in

clud

e fa

ilure

s in

prim

ary

site

.

Dat

a gi

ven

for m

ore

prec

ise

site

s ar

e no

ted

as s

uch.

cann

ot b

e gi

ven

beca

use

the

stat

us o

f th

e pr

imar

y in

the

neck

recu

rren

ces

is n

ot k

now

n.

’


lesions of the tonsillar fossa, the examination of the neck can be 11 % false positive and 50% false negative (Terz and Farr, 1967). In Terz’s series, only the the histologically positive neck truly affected survival, emphasizing that the significance of clinically positive nodes cannot be assessed without confirmatory microscopy. In our experience, clinical positive adenopathy has always been accurate when more than one level is involved. In the Perez (1972) series, the survival with one node was 60% and two nodes decreased 5-year survival t o 9%. Both Wang and Terz have indicated that T3 lesions fail significantly with irradiation and surgery alone.

Table VII. Patterns of Recurrence in Epidermoid Carcinoma of the Base of the Tongue

The series in Table VII reveal high survival rates and may not be representative. Most series survival rates are 10% but they do not give sites of failure.

Harrold (1967) noted that local failure was the major problem. The site of his surgical failures appeared to be in the endolarynx.

Base of tongue, with its high incidence of clinical and subclinical adenopathy and its deeply invasive profile going into hyoid and endolarynx in a high percentage, yields poor control rates and survival. The highly dysfunctional procedure which is necessary to surgically extricate this disease and its nodal component appears to have deterred surgical attack except for irradiation failure.

Table VIII. Patterns of Recurrence in Epidermoid Carcinoma of the Pharyngeal Wall

There is a scarcity of articles dealing with this region. Minimal information is available relating to patterns of recurrence. The high incidence of involvement of retropharyngeal nodes has been emphasized (Fletcher and Jesse, 1962) which indicates the futility of hoping to control the disease by surgery alone. Lead- better (1970) has shown that surgery and irradiation give recurrence rates which are equal t o each other, approximately 36%, but the recurrence pattern is different for x-ray (3: 1, primary: lymph node) and surgery (1 :3, primary: lymph node). The negative neck cases have about the same survival as those with positive nodes on admission. Wilkins (1971) salvaged 5 of 8 patients with carcinoma of the pharyngeal wall with surgery (vertical pharyngotomy). The reasons for this high survival and low recurrence rate are discussed by the author.

Table IX. Patterns of Recurrence in Epidermoid Carcinoma of the Laryngopharynx

General

Survival of hypopharyngeal lesions is dismal with irradiation or surgery

Tabl

e V

II.

Patte

rns o

f R

ecur

renc

e in

Epi

derm

oid

Car

cino

ma

of t

he B

ase

of t

he T

ongu

e

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Patie

nts

Prim

arie

s N

odes

N

odes

N

odes

N

odes

N

ode

Alo

ne

Rec

urre

nce

5 Y

ear

Flet

cher

(19

62)

59

N.A

. N

.A.

N.A

. N

.A.

N.A

. 11

/6

68

31

Surg

ery

Har

rold

(19

67)

244

50a

60

23

184

25

1271

15

90

25

aMor

e th

an h

alf

of to

ngue

.

Tab

le V

III.

Patte

rns o

f R

ecur

renc

e in

Epi

derm

oid

Car

cino

ma

of t

he P

hary

ngea

l Wal

l

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y/

%

%

No.

A

dvan

ced

Lym

ph

of N

eck

Posi

tive

Lym

ph

Lym

ph

Prim

ary

Surv

ival

R

adia

tion

Patie

nts

Prim

arie

s N

odes

N

odes

N

odes

N

odes

N

ode

Alo

ne

Rec

urre

nce

5 Y

ear

Wan

g (1

971)

37

38

15

N

.A.

22

19

19/N

.A.

N.A

. 25

a Fl

etch

er (

1962

) 38

N

.A.

N.A

. N

.A.

N.A

. N

.A.

10/2

83

40

L

eadb

ette

r (1

970)

10

7 56

41

0

66

73

29/1

0 75

21

Su

rger

y St

efan

i (19

71)

Lea

dbet

ter (

1970

) 18

5 84

55

N

.A.

39

69

20

0 13

0 63

16

813

92.5

9.

1 19

79

61

8 43

21

aThi

rd y

ear

surv

ival

for W

ang

(197

0).

Tab

le IX

. Pa

ttern

s of R

ecur

renc

e in

Eoi

derm

oid

Car

cino

ma

of th

e L

arvn

zooh

arvn

x

No.

N

o.

Clin

ical

ly

No.

N

o. w

ith

%

Rec

urre

nce

%

Neg

ativ

e C

onve

rsio

ns

Clin

ical

ly

Adv

ance

d Pr

imar

y %

%

N

o.

Adv

ance

d L

ymph

of

Nec

k Po

sitiv

e L

ymph

L

ymph

Pr

imar

y Su

rviv

al

Rad

iatio

n Si

tes

Patie

nts

Prim

arie

s N

odes

N

odes

N

odes

N

odes

N

ode

Alo

ne

Rec

urre

nce

5 Y

ear

Stef

ani

(197

1)

Lala

nne

(197

1)

Jorg

ense

n (1

970)

T

aski

nma

(196

9)

Flet

cher

(1

970)

D

effe

bach

(1

972)

Li

egne

r (1

965)

Li

egne

r (1

965)

Lede

rman

(1

967)

Jo

rgen

sen

(197

0)

Hyp

opha

rynx

Rid

ge

Supr

aglo

t tic

Supr

aglo

ttica

Supr

aglo

ttic a

nd

Rid

ge

Supr

aglo

ttic

Epig

lotti

s

Rid

ge (

excl

ude

Epig

lotti

s and

H

ypop

hary

nx)

Hyp

opha

rynx

Glo

ttic

215

108

60

395

115

100 8 15

673

171

84

69

50

20

45

55 0 0 N

.A.

31

47

N.A

.

41

231 N.A

.

54 5 N

.A.

284

167

N.A

.

N.A

.

N.A

.

53

N.A

.

N. A

.

2 N.A

.

N.A

.

N.A

.

116

N.A

.

19

164

N.A

.

46 3

N.A

.

419 4

75

N.A

.

N.A

.

66

N.A

.

53

N.A

.

N.A

.

N.A

.

N.A

.

1681

1 1

N.A

.

N.A

.

1031

55

37lN

.A.

55lN

.A.

1 1N

.A.

2lN

.A.

N.A

.

N.A

.

N.A

.

N.A

.

N.A

.

66

N.A

.

N. A

.

-

N.A

.

N.A

.

N.A

.

8 21

51

45

61

35

63 6.7

11

68

TA

BL

E IX

(Con

tinue

d)

Pere

z (1

968)

Glo

ttic

91

Lieg

ner

(196

5)

Task

inen

(1

969)

La

lann

e (1

971)

La

lann

e (1

971)

Surg

ery

Flet

cher

(1

970)

B

ryce

(1

971)

N

orris

e (1

967)

Tu

cker

(1

971)

Le

roux

- R

ober

te

(196

5)

Glo

ttic

23

Glo

ttic

179

Hyp

opha

rynx

20

7

Endo

lary

nx

134

Supr

aglo

t tic

10

3 R

idge

En

dola

rynx

93

0 44

% G

lotti

c on

ly

64%

Sup

ragl

ottic

10

0 (n

o G

lotti

c)

Endo

lary

nx

81

Endo

lary

nx

1000

H

ypop

hary

nx

0 0 33

79

37

75

36

N.A

.

N.A

.

N.A

.

N.A

. N

.A.

N.A

. N

.A.

N.A.

N

.A.

162

N.A

. 17

N.A

. N

.A.

N.A

.

N.A

. N

.A.

N.A

.

N.A

. N

.A.

0 N.A

.

N.A

.

N.A

. N

.A.

N.A

. N

.A.

N.A

. N

.A.

N.A

. N

.A.

N.A

. N

.A.

N.A.

N.

A.

N.A

. N

.A.

N.A

. N

.A.

N.A.

N

.A.

N.A

. N

.A.

181N

.A.

11N

.A.

28/1

3

N.A

.

N.A

.

16lN

.A.

288/

N.A

.

1218

19/1

0

128/

88

N.A

. N.

A.

68

N.A

.

N.A

.

N.A

.

N.A

.

60

66

60

N.A

. 94

71 9 46

54d

50

63

N.A

.

36'

~~~

~ ~~

~

aGen

eral

ly r

adia

tion

for

early

lesi

ons

and

surg

ery

or c

ombi

ned

trea

tmen

t fo

r adv

ance

d le

sion

s.

bRid

ge is

def

ined

as

supr

ahyo

id e

pigl

ottis

and

ary

epig

lotti

c fo

ld.

CLa

rge m

ajor

ity d

ied

of in

terc

urre

nt d

isea

se o

r a s

econ

d pr

imar

y.

I NED

2 ye

ars.

eI

nclu

des

radi

atio

n co

mbi

ned

with

sur

gery

or r

adia

tion

alon

e.


alone (Baclesse, 1949; Lalanne et al., 1971; Lederman, 1967). When ridge lesions are defined distinct from hypopharyngeal lesions the survival is better for ridge lesions (Fletcher et al., 1970; Lalanne et al., 1971 ; Liegner and McCuaig, 1965).

True endolaryngeal lesions have the best survival (see Table IX). Survival depends on size in supraglottic and ridge lesions but not in carcinoma of the hypopharynx. The neck should be treated electively in supraglottic and ridge lesions and if not, survival is diminished (Norris, 1967).

decreases survival by at least threefold (Deffebach and Phillips, 1972; Jorgensen, 1970).

In carcinoma of the vocal cords and supraglottic region positive adenopathy

Supraglottic

at the primary site or primary site and neck occur equally in both surgical and irradiation series ( 2 : l) , but for different reasons. The failure with irradiation occurs at the tumor center whereas with surgery the recurrence occurs at the pharyngeal anastomosis due to inaccurate assessment of tumor extent. Lymph node metastases is often histologically bilateral when only clinically unilateral. Thus surgery fails in the contralateral neck whereas irradiation alone usually fails, because of large lymph node size.

Lalanne (1971) states that size of the primary mainly influences 5-year survival: 55%in the early lesions and 22% in the more advanced. Taskinen (1969) showed that only the TI NoMo lesion responded successfully to irradiation alone, whereas all other stages were controlled best by combined therapy. Deffebach (1972), employing irradiation alone, discounted the importance of the size of the primary. His series emphasized the 5-year survival importance of cervical lymphadenopathy: 70% No and 1 5% N,.

favored because the surgical alternative was a laryngectomy. Irradiation followed by total laryngectomy and neck dissection(s) for salvage for early nondestructive lesions with or without cervical adenopathy has been the general regime (Bryce and Rider, 1971; Deffebach and Phillips, 1972). It is impossible to assert at this time how supraglottic laryngectomies will affect this philosophy.

The survival in supraglottic carcinoma varies from 35 t o 60%. Recurrences

Before the popularity of the supraglottic laryngectomies, irradiation was

Glottic

All cancers of the vocal cords which are confined to the endolarynx should be cured. In patients who die of their disease distant metastases is small compared to the nearby supraglottic carcinomas whose incidence of distant metastases is 25% (Taskinen, 1969).

The significant recurrence rates in Table IX result from two therapy patterns: 1. voice saving surgical procedures in T I lesions, and 2 . radiation


therapy with surgical salvage in T2 and T3 lesions. It is not our purpose to criticize these patterns because not only do we

practice them but also because the cured patient encourages us to take the risk. Morrison (1 971) with irradiation alone demonstrated that survival in the

TI NoMo cordal carcinomas was 84% and dropped to 6% in the T4NoMo lesion. Perez (1 968) and Fletcher (1 972) emphasize the relatively poor prognosis

of anterior commissure and subglottic involvement. Both Morrison (1971) and Taskinen (1969) emphasize the poor success in

the irradiated cancer which causes immobility of the cord. Unrecognized muscle invasion with mobile cord tumors is purported to be the cause of local irradiation failure (Morrison, 1971).

HYPOPharYnx

Survival is not apparently related to tumor size or the form of treatment. Lalanne (1971), employing combined therapy, reported 18% survival with early lesions and 16% survival with late lesions.

Baclesse (1 949) reported a 6% survival with irradiation. Baclesse admitted that control of the primary was the major therapeutic problem whether the nodes were clinically positive or negative. Stefani (1971) confirmed the aggressive nature of the primary and further demonstrated the appreciable incidence of distant metastases and second primary cancers.

are the result of inclusion of ride lesions under hypopharynx. We feel that the better results of Leroux-Robert (1965) and Norris (1967)

Table X. Recurrence Pattern in Metastatic Cervical Adenopathy

In the clinically positive neck, surgery combined with irradiation or surgery alone appears to have a superior control rate when compared t o irradiation alone. Whether irradiation is as good as surgery in the clinically negative neck which has a high probability of having microscopic metastases needs to be investigated.

Opinion is divided as to what clinicopathologic facts are important in cervical adenopathy. Certainly much confusion exists because investigators do not distinguish between control rates and survival.

Beahrs (1 962) feels that in lesions of the oral cavity, the level of the adenopathy affects control rate. Barrie (personal communication) claimed control in 86% of negative necks with a 51% survival. Whereas control rates were similar at all levels in his series, survival was 30% at Level I1 and dropped to 19% at Level IV. Barrie (1970) and Farr (1972) recommended not doing radical neck dissection for disease at level IV and V because of poor survival.

with nodes greater than 3 cm did he feel that combined therapy offered a decreased recurrence rate over surgery alone. Farr (1972) and Strong (1966) feel

Lindberg (1968) states that the size of the lymph node is important; only

w 4

P 2

TAB

LE X

Rec

urre

nce

Patte

rn I

n M

etas

tatic

Cer

vica

l Ade

nopa

thy

U z

No.

with

%

C

linic

ally

N

o. w

ith

%

No.

Fa

ilure

-

Neg

ativ

e C

linic

ally

A

dvan

ce

Lym

ph

in

%

5

Trea

t- L

ymph

Po

sitiv

e Ly

mph

N

ode

Posi

tive

Surv

ival

a

3F

Aut

hor

Site

m

ent

Nod

es

Nod

es

Nod

es

Failu

re

Nec

k 5

Yea

r (u

B Li

ndbe

rg (

1968

) O

roph

aryn

x SC

20

11

8 60

30

25

5

(u

Lary

ngop

hary

nx

C

12

130

80

21

16

Flet

cher

(19

72)

Oro

phar

ynx

C

N.A

. 15

5 62

15

9.

8 23

46

B

eahr

s (1

962)

O

ral c

avity

S

85

530a

N

.A.

121

Wiz

enbe

rg (1

972)

O

ral c

avity

X

N

.A.

109

87

11

10

26

Stro

ng (1

972)

O

ral c

avity

C

28

83

N

.A.

N+2

6b

31

Oro

phar

ynx

Lary

ngop

hary

nx

Oro

p har

ynx

N-0

La

ryng

opha

rynx

Oro

phar

ynx

N-

35

Bar

rie (

1970

) O

ral c

avity

S

250

552

N.A

. N

+255

b 46

N

+25

Lary

ngop

hary

nx

N-5

1 V

otav

a (1

972)

C

N

.A.

75

N.A

. 15

20

N

.A.

Wan

g (1

972)

A

TP a

nd R

MT

X

20

23a

0 16

70

N

.A.

Wan

g (1

972)

T

F

X

0 20

a 0

4 20

N

.A.

Mus

tard

(19

63)

Ora

l cav

itv

S 10

27

0 31

46

17

32

aClin

ical

ly a

nd h

isto

logi

cally

pos

itive

. bN

+ =

pos

itive

nod

es;

N-

= n

egat

ive

node

s.

‘S,

surg

ery;

C, c

ombi

ned;

ATP

, ant

erio

r ton

silla

r pi

llar;

RM

T, re

trom

olar

tong

ue; T

F, to

nsill

ar f

ossa

; X, i

rrad

iatio

n.

37 5 Recurrences in Head and Neck Cancer

that the addition of irradiation to all histologically positive necks significantly decreases recurrence rate. Yonemoto (1 972) indirectly confirms this since he observed 20 failures outside the surgically treated neck area in 51 patients who failed regionally. It is reasonable to assume that post-operative irradiation may have prevented some of Yonemoto’s failures.

Table XI. Salvage of Failures

No. No. Total Regional No.

Author Sites Cases Failures Salvaged

Fayos (1969)

Saxena (1970)

Pierquin (1971)

Kuhn (1970)

Spiro (1971)a

C o m a (1967) Cady (1969)a Crews (1971) Crews (1971) Krishnamurthi (1971 ) Wang (1972) Ballantyne (1967) Fayos (1971) Bryce (1971) Lalanne (1971)

Tucker (1971) Perez (1968) Taskinen (1969) Liegner (1965) Deffebach (1972) Fletcher (1970)a

Fletcher (1970)

Taskinen (1969) Lalanne (1971)

Lalanne (1971 Wizenberg (1972)

Anterior 213 tongue Anterior 213 tongue Anterior 213 tongue Anterior 213 tongue Anterior 213 tongue Floor of mouth Lower gingiva Lower gingiva Buccal mucosa Buccal mucosa Tonsil region Tonsil region Tonsil region Endolarynx Intrinsic larynx Infrahyoid Epiglottis Endolarynx Glottic Glo ttic Epiglottic Supraglottic Supraglottic and ridge Supraglottic and ridge Supraglottic

80

41 9

245

262

145

157 320 42 85

974 232 320 102 98 74

81 91

179 8

103

115

54 No

30

274

145

121

70

N.A. 85 19 21

528 132 227

60 56 23a

29 18 41

1 15 16

37

395 156 Ridge and suprahyoid 60 1 9a epiglottis Hypopharynx 117 52 Salvage of neck 109 49 fund., oral, cavity, and tonsil

3

44

30

16

1

8 26

7 8

88 25

8 9

15 10

6 8

12 1 6 1

19

4 2

5 2


Table XI. Salvage of Failures

Table XI demonstrates a clear example of the ohcologist’s inability to salvage a failure of either surgery or radiation therapy in all anatomic sites. We feel this is due to two major causes. The first is the extreme difficulty in de- tecting early recurrence until it becomes unresectable. The second is that the biological aggressiveness of the tumor is the cause of the recurrence, not merely failure due to performance of a specific method of treatment. This fact is borne out by the high incidence of distant metastases in tumors that regionally occur after treatment failure.

The average salvage for all the series listed in Table X is 16% of all regional failures.

Table XII. Conversion from Negative Neck and Salvage

Most of the patients reported in Table XI recurred in the primary site at the time of conversion. Fayos (1972) reported 43 conversions, only 4 of which recurred in the nodes alone. His low incidence of conversions (43 of 203) probably reflects the fact that the jugulo-digastric node was always irradiated in continuity with the primary. Farr (1972), in a surgical series of oral cavity and oropharyngeal primaries, found only 33 patients dying of nodal disease alone in 300 patients with clinically negative neck. He emphasizes the biological aggressiveness of carcinoma in patients that recur by showing that survival in these patients approaches the same survival as those patients who present with clinically positive nodes: about 30%. Mustard (1963), in an oral cavity series treated with irradiation, had a 17% survival with a clinically positive neck, 33% for patients who converted in one year and 5 1 % who converted in more than one year.

In our opinion, recurrence in the primary site is the most common cause of conversion.

Table XII. Conversion from Negative Neck and Salvage

Total No. Number Con- No.

Author Site Cases versions Salvage

Fayos (1972) Tonsillar region 206 43 16 Alford (1958) Floor of mouth 29 4 3 Harrold (1971)a Floor of mouth 772 137 18 Campos (1972) Floor of mouth 76 13 10

alncludes irradation.


CONCLUSIONS

We are somewhat distressed by the recent emphasis on the treatment of the neck in tumors of the aerodigestive tract. The single most important factor, we feel, is the primary site and treatment should be designed to treat the primary site with less concern directed to the clinically negative or positive neck. Although we feel that surgery is niore effective in the clinically positive neck, the biological significance of the clinically positive neck, initially or in future, reflects t o a large degree the aggressiveness of the primary tumor and its propensity t o recur after either surgery or irradiation.

Early nodal disease or a high percentage of conversions may be seen with early carcinomas of the mobile tongue, tonsillar fossa, or supraglottic regions. It is in these patients that the primaries yield to irradiation whereas the neck adenopathy may persist. In the other areas, positive adenopathy is often associated with an advanced primary.

When the nodes are advanced the primary at all anatomic sites is often difficult t o control.

In general, surgery after irradiation for persistent cervical adenopathy should include the primary site.

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Recurrence patterns in squamous cell carcinoma of the oral cavity, pharynx, and larynx

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