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ABSTRACT:

Am Roenigenol 12 6 : 1082-1087, 1976

1082

A D JU V A N T C H E M O IM M U N O T H E R A P Y IN A D V A N C E D

L E S IO N S O F T H E H E A D A N D N E C K

F R E D E R I C K R . E ii.n t’ A N D D O N A L D L . M ow ro c’

G ro w th o f m aligna n t tu m o rs o f the h ea d an d ne ck ha s b ee n a ssoc ia ted w ith p ro -

g ress ive im pa irm en t o f im m u no log ic ac tiv ity . S u cc e ssfu l co n tro l o f d ise ase ha s b e en

sho w n to rev erse th is de fe ct. P re lim ina ry re su lts o f a no nra nd om iz ed tria l red uc ed

re cu rren ce o f h ea d a nd n ec k c a nc er fo r a m e d ia n tim e o f I I .5 m on ths in eigh t o f 10

p atien ts w h o rec e ive d c he m o im m u no the ra py ad ju va n t to su rg ic a l re sec tio n o r

ra d ia tio n trea tm en t. T he nu m b er o f p atie n ts in th e serie s w a s sm all an d th e fo llo w -

u p tim e to o sho rt to de te rm in e th e le ng th o f e ffec tiv en ess fo r th is tre a tm e n t. B ase d

o n th ese resu lts , a n ew p ro to co l ha s be e n in itia ted to ran do m iz e pa tie n ts w ith a d -

va nc e d T 3 a nd T 4 le sion s in to g ro up s fo r co m p a riso n o f a d ju va n t c he m oth era py

a lon e w ith a d ju va n t c he m o im m u no the ra py .

INTRODUCTION

T h e c on ce p t o f ho s t re s is ta nc e a s an im po r-

tan t fac to r in b o th th e inc ep tio n an d pro -

g ress io n o f h ea d a nd ne ck m a lig na nc y ha s

b ee n p ro po sed fo r m a ny y ea rs . I t o rig ina tes

fro m o bserv a tion s o f th e u np red ic tab le

clin ic al c ou rse fo r p atien ts w ith tum ors in

the se a na to m ic lo ca tio ns . W h ere a s som e

pa tie n ts ha ve a ra p id rec u rre nc e o f d ise ase

de sp ite a pp are n tly a de qu ate trea tm en t fo r

ea rly tu m o rs, o th e r p atien ts de m o nstra te a

re la tiv ely slow p rog ress io n o f d ise ase de -sp ite fa r-a dv an ce d m a lig na nc ies .

G ro w th o f m a lig na n t tu m o rs o f the h ea d

a nd n ec k h as be en a ssoc ia ted w ith p ro g re s-

sive im p airm e n t o f im m uno lo g ic re ac tiv ity

[I]. A n er g y h as be en ob se rve d in pa tie n ts

p rio r to the d ev elopm e n t o f c ac he x ia a nd

m a lnu tritio n , e ve n w itho u t w id esp rea d

v isc e ra l a nd bo ne m a rro w in vo lve m e n t.

T he im m u no log ic im pa irm en t no te d in

c an ce r p atie n ts w as no t a de fec t th at p re -

c ed ed th e de ve lop m e n t o f m a lign an c y

be ca u se it co u ld be re v erse d if suc ce ssfu l

co n tro l o f d ise ase w a s ac h iev ed [2 -4 ] . O pt i -

m is tic a lly , the n , it m ig h t be p oss ib le to

au gm e n t the im m u no log ic re a ctiv ity o f the

c an ce r p a tien t. H ow ev e r, a dd ition a l re-

p o rts ha v e sh ow n th at th e th era pe u tic

m od ali tie s u sed to trea t ne op lasm s o f the

he ad a n d n ec k a re th em selve s im m u no -

sup pre ss ive . T he su ppre ss ive e ffec ts o f

s u rge ry [ an d ch em o the rap y [6 ] ap pe ar to

be o f re la tive ly sho rt du rat ion ; the im -

m un osu pp ress ive effe c ts o f ra d io th era py

[7 , 8 ] m ay o r m ay n o t be m o re p ro long ed

[9 -I I ]. T h u s it w ou ld see m tha t if im m u no -

lo g ic rea c tiv i ty co u ld be m ain ta ine d d urin g

tre atm e n t, a g re ate n th era pe u tic b en efi t

m igh t be a c h ie ve d .

W hile im m u no the ra py fo r tre atm e n t o f

m align an cie s in lab o ra to ry a n im als a s w e ll

as fo r m a lign a n t m e lan om a in m an ha s

be en sho w n to b e e ffe ctive its u se is

lim ite d . In la bo rato ry an im a ls it w as o f

be ne fit w he n th e tum or bu rd e n w a s in a

ra t io o f a pp rox im a te ly I07_108 cel ls [12] ;

la rge r a m o un ts o f tu m o r rare ly re spo nd ed

to im m un o lo g ic m a n ip u la tio n . T h ese sam e

prin cip le s se em to b e a pp lic ab le in m a n . A

the rap eu tic e ffec t w a s ge n era lly a ch ie ve d

in p at ien ts w ith su bc lin ica l d isea se [13 ]

w he re as fo r m ore ad va nc ed d isea se , re su ltsw ere n o t n e arly a s im p ress iv e [14] . If im -

m u no the ra py is ap p lied to the tre a tm e n t o f

pa tie n ts w ith tu m o rs o f th e he ad a nd n e ck ,

T h e se inve stig ation s w e re sup porte d by gra n ts from the U .S . P u blic H ea lth Serv ice (C A 1258 2) an d fr om S u r g ic a l S erv ic es, S epu l-

ve d a V ete ran s A d m in istr a tion H o sp ita L

1 D iv is ion o f O n co logy , D ep artm e n t o f S u rg er y , U C L A C e n ter for th e H ea lth S cie n ce s , Lo s A ngeles, C a lifo rn ia oo2 a nd S ur gic al

S e rv ices , S ep ulv eda V e terans A d m inis tra t ion H ospita l S e pulved a, C a lifo rn ia 91343 . A d d r e s s rep r in t req ue sts to the D iv isio n o f

O ncology .



C H E M O IM M U N O T H E R A P Y IN H E A D A N D N E C K L E S IO N S 1083

it c an no t be use d a s a p rim a ry tre a tm e n t

m o da lity bu t ra the r a s a n ad juv an t to th e

e x ist ing the ra pe u tic m o da lities o f su rge ry ,

ra d ia tion , an d c h em oth e ra p y .

P re lim ina ry rep o rts from D o na ld so n

[ 15 , i6 ] h av e sh ow n tha t a g re a te r the na -

pe u tic resp on se w a s ac h ie v ed in he ad an d

n ec k p atien ts w h en B C G , a no nspe c ific im -

m u ne s tim u lan t, w a s c om bin ed w ith ch em o -

the rap y (m e th o tre xa te ) tha n w he n c he m o-

th era py a lon e w as use d .

T h is pa p er d e sc rib es a pha se I p ilo t study

d es ig ne d to de te rm in e the effe c t o f B C G

im m un o th era p y in c om bina tio n w ith

m e th o tre xa te . T h is reg im en w as e va lua te d

in p a tien ts w ith recu rren t m a lign an t d isea se

of the he ad a nd ne ck a nd in p atie n ts w ith

a dv a nc ed le s io ns w h o h ad a n 8o ch an c e

o f re c u rre nc e w ith s tan da rd m o de s o f

therapy.

S U B JE C T S A N D M E T H O D S

T he 20 pa tie n ts iR v es tiga ted w ere ev alu a ted

e ith er in th e D ep a rtm e n t o f S u rg e ry , D iv is io n

o f O n c o lo gy , U C L A S c ho o l o f M e d icin e , o r the

S epu lveda V ete rans A dm in istra tion H o sp ita l,

S e pu lv ed a, C a lifo rn ia . T he y ra ng ed in ag e fro m

29 tO 73 y e ars . A ll ha d a dva n ce d ‘F 3 or

squ am o us ce ll ne op lasm s of the he a d a nd n ec k

reg ion an d ha d no h isto ry o fp rio r m a lign a nc ies

o r e v id e nc e o f w id esp re a d tu m or b efo re a d -

m in istratio n of chem o im m u no th erapy . P a -

tie n ts w e re c lin ica lly e va lu ate d b y c om ple te

p hys ica l exam ina tion , chest x -ray , an d liv e r,

b ra in , a nd b on e sc a n p rio r to en te ring the s tu dy .

H isto log ic con firm a tion of sq uam o us C eil ca rc i-

n o m a w as o b ta ine d in e ve ry c ase .

T he ex pe rim en ta l na tu re o f the p ro ce du res

w a s ex p la in ed to ea ch pa tie n t p rio r to e n terin g

th e s tud y a nd a s ig ne d co nse n t w a s ob ta ine d .

P a tie n ts w ere d iv id ed in to th ree c a teg o rie s :

tho se w ho h ad fa ile d o n all p rev iou s the ra py

a nd h ad e s ta b lish ed d isea se (ta b le x ) ; and tho se

w h o d id no t h av e clin ic al ly e v ide n t d ise a se b u t

w h o w ere trea te d p rop hy la ctica lly fo r sub -

c lin ic al d ise ase fo llow ing rad ia tion th era py

(table 2) or su rge ry an d rad ia tio n the rap y

table 3 .

T h e c he m o the ra pe u tic d rug m e tho tre xa te

( o m g /m 2) w as a d m in is te red o nc e a w ee k fo r

I m on th an d e ve ry o th er w e ek the rea fte r fo r

the du ration o f th e s tud y . Im m un o th e ra p y

w a s a cc om plish e d w ith B C G T ice s tra in from

C hic ag o R e se a rch , a dm in is tere d by the T in e

te ch n iq ue to the ax illa e an d bo th g ro in s ev e ry

w ee k fo r 3 m o n th s a nd the n ev ery o th er w e e k

fo r the du ration o f the s tu dy . F o llow -u p ex am i-

n ation w a s pe rfo rm e d ea c h m o n th .

A c om ple te resp on se to ch em othe rap y w as

d efine d a s th e d isap pe ara n ce o f a ll v is ib le d is-

e a se an d no ev id en ce o f ne w d isea se fo r a

p eriod o f 2 m on ths. A pa rtial re spo nse w as de -

fin ed a s o re du ction in e s tab lishe d d ise ase

and no new lesion s. W h ile su rg ical p roced ures

d iffere d fo r e ac h pa tie n t, the y ba s ic ally in -

c lud e d e n b lo c re sec tio n o f th e p rim a ry tu m or

a nd reg ion al ly m ph no de s . X -ra y trea tm en t

w a s g iv en us in g c ob alt 6o te le th era py at a

d osa ge o f oo o -6 ,o oo rads o ve r 6 w eeks.

Im m uno log ic eva lu atio ns o f de layed cu tane -

o us hy pe rsen s itiv ity w ere pe rfo rm e d w ith top i-

c al ly ap p lie d d in i troc h lo rob en z en e (D N C B )

and a ba ttery o f reca ll an tig en s. R eac tions w ere

re co rde d a fter 48 h r. S eria l D N C B sk in te s ting

w as p erfo rm ed a t m on th ly in te rva ls [J. A

hy persens itiv ity sco re w as ass igned to each

te s t, an d a sc o re o f 3 o r g re ate r w as c ons id e red

pos i t ive [17] .

R E S U L T S

T a b le I sh ow s th e re su lts o f ch em oim -

m u no the na py in s ix p at ien ts w ith es ta b -

l ishe d re c u rre n t d ise a se . A c o m p lete n e-

sp on se to c he m oim m u no th era py w a s ob -

ta m ed in o n ly on e pa tie n t , n o . i. T h is pa -

tie n t ha d ree x cis io n o f th e p rim ary tum or,

m a x illary a n tru m , a nd o rb it m on th s a fter

in itiatio n o f chem oim m un o the rap y an d has

b ee n free o f d ise a se 6 m on th s fo llow in g th is

su rge ry . M icro sco p ic re s idu al d ise ase w as

p rese n t in th e op era tiv e sp ec im en . P a tie n ts

2 an d 3 ha ve m ain ta ine d a o re duc t ion

in tum o r size fo r and 5 m o nths, re spec -

t ive ly . B o th pa tie n ts ha ve c lin ica lly e v id en t

res id ua l d ise a se bu t h av e no t de ve lop ed

ne w le s ion s. T he re m ain ing th re e p at ien tsd id no t ha ve a ny m ea su ra b le d ec rea se in

tum or s iz e , an d a ll e xp ire d .

S im u lta ne ou sly , w e be ga n a no nna n do m -

ize d p rosp ec tiv e s tud y of th e B C G -m e th o -

trex ate co m b in atio n a s a d ju va n t tre a tm e n t

to ra d ia tio n o r su rge ry . T a b le 2 sho w s the

resu lts o f trea tm en t w ith a d ju va n t c he m o-

im m u no the rap y fo r s ta ge T 3 a nd T 4



N o ra .-N on e of th e se p atien ts w ere tr ea te d su rg ic a lly .

1084 E IL B E R A N D M O R T O N

T A B L E

C H E M O IM M U N O T H E R A P Y IN P A T IE N T S W IT H E S T A B L IS H E D R E C U R R E N T D IS E A S E

Locat ion of

P atie n t A ge P rim a ry M alig nan t D ate o f X -ray D ate o f C h e m oim m u n o - R esp on se F o llo w -u p

N o. (Y r ) T u m or N ec k N o d es O p er a tion T h er ap y R ec u rr en c e th e ra p y ( ) ( M o )

I 6 Antrum - IO/’74 P reO p 4 /’7 4 M tx , B C G 10 0 6

and 8 /’73

in tra- I

cranial

2 7 3 T em p o r a l 4/1 2 I2 /’74 P o stO p I/F 75 * M tx , B C G o 4

bone 12/’74

3 54 R et r o m o l a r 10 /I 5 8 /’74 P o s t O p 10/174* M tx , B C G o9 /174

4 62 Larynx 4 /10 8 /’74 P o stO p 12/’74 M tx , B C G o 39/174

5 6 i T o nsil + . . 8 /’73 I2 /’73 M tx , B C G o 3

6 5 T o n g u e + . . . 8 /’73 Io /’73 M tx , B C G o 2

base

I Dur i ng x-ra y th er ap y.

squ am ou s c e ll ca rc ino m a of the he a d an d pa tie n ts ha d po stop era tiv e ra d ia tio n the n -

n e ck in w h ich rad ia tion th era py w a s th e ap y to the tum o r b ed a nd the re g io na l

p rim ary m od ality . O f the fou r pa tien ts lym pha tic s excep t fo r pa tien ts 4 an d w ho

tre ate d th us far, th re e a re free o f re cu rren t w ere op era te d on afte r ra d ia tio n th era py

d isea se a fter a m ed ia n o f 6 m o n th s . O n e fa ilu re .

p atien t h ad ra p id re cu rren ce de sp ite ra d i-

a tio n a nd ch e m o im m un o the rap y a nd cx - Toxici ty

p ired w ith in 4 m on ths o f on se t o f trea t- F o r s ix o f th e 14 pat ien ts (40 ) t rea ted

m en t. A ltho ugh the fo llow -u p tim e is w ith ad ju van t ch em oim m un o the rap y , it

re la tive ly sh o rt fo r the se p atien ts , th e ir w a s n ec e ssa ry to d ec rea se the sc he du le d

c lin ica l resp on se ha s be e n d ram a tic . d osa ge o f m e tho tre xa te . T he m a jo r tox ic

A serie s o f io p atien ts w a s tre ated w ith e ffec t w a s he m ato po etic , m a n ife s ted b y

ad juv an t c h em oim m un o th era py fo llow in g w hite ce ll co un ts low e r tha n 2 ,000 . T h e de -

su rg ica l ex cis ion of all g ross tu m or p lus lay in treatm en t w as n ev er m ore than i

rad ia t ion the rap y (ta b le 3 . E igh t o f th e 10 w e ek . N o inc id en ce o fre na l tox ic ity , se ps is ,

( 8o ) are a live and free o f recu rren t d is- o r pe rm anen t bon e m arrow tox ic ity w as

ea se after a m e d ian o f i i . m o nth s . A ll o bse rv e d . O ra l u lc era tio n w as ob se rv ed in

T A B L E 2

C H E M O IM M U N O T H E R A P Y A S A D JU V A N T T R E A T M E N T T O R A D IA T IO N T H E R A P Y

Locat on of

P a tien t A ge Pr imary M align an t X -R ay T h er ap y C h em oim m u n o- F o llow -u p

N o . (Y r ) T u m o r N ec k N od e s (R ad ) th e rap y S ta tu s (M o)

I 6 8 R e trom o lar + s ,o oo M tx , B C G N .E .D . 4

2 48 T ong ue base + 5 , 000 M tx , B C G N .E .D . 8

3 47 T on gue ba se - 5 ,o oo M tx , B C G N .E .D . 6

4 6 L a r y n x 5 , 000 M t x , B C G E xp ired 4

(r u r re nc e )



1086 E IL B E R A N D M O R T O N

o ur o p in ion , th e B C G -m etho trex ate c om -

b ina tion app ears to h ave lim ited v alu e fo r

th is type of pa tien t. O n ly one of six pa -

tien ts ach ieved a co m ple te re spo nse , and

th a t ha d to be fo llo w e d by fu rthe r su rg ic a l

in te rve n tio n . T h us i t a pp ea rs u n like ly tha t

c om plete tu m o r de s truc tio n w a s e ve r

a c h ie ve d .

T h e re su lts o f c he m o im m u no the ra py a s

ad ju van t to su rge ry o r irrad ia tion w ere

m u ch m o re im pre ss iv e . S in ce , s ta tis tic a lly ,

8 o o f the se p atien ts w ou ld deve lop re -

c u rre n t d ise ase , re sidu al sub cl in ic a l d ise a se

w a s ve ry like ly p re sen t a t th e c om pletion

o f su rg ery an d /o r rad ia t ion th era p y . T he

fa vo rab le re su lts re po rted he re m ust be

te m pe red by the fac t tha t th is w a s n o t a

ra n dom iz ed tria l n o r d id it inc lu de c on -

se c u tiv e pa tie n ts ; a lso , the du ration o f the

s tu dy w a s re la tiv ely sho rt. H o w ev er, the

re su lts a re encourag ing since th e c lin ical

c ou rse o f pa tie n ts w ith a dva n ce d tu m o rs o f

th e he a d an d n ec k is re la tiv ely c on s ta n t.

T he m e d ia n tim e to rec u rre nc e in sev era l

se rie s is ap p ro x im ately 8 m o n th s . A m uc h

lon ge r fo llo w -up tim e is o bv iou s ly re qu ired

b efo re th e a c tua l ou tco m e fo r the se pa -

tien ts c an b e d e term in ed . H o w e ve r, it d oe s

a pp ea r th at the p roc e du re o f c he m o -

im m un o th era py is w ell to lera te d w ith a c-

c ep ta b le tox ic ity a nd th at it d e cre ase s th e

re cu rren c e ra te , a t le as t b ase d on the sho rt-

te rm fo llow -u p of the se pa tie n ts . W he th er

th e d ise ase w ill e ve n tu al ly re c u r rem a ins

to b e see n .

In ad d ition , the qu es tio n rem ains o f

w h ethe r B C G im m un o th era py c on tribu te d

to the ch em othe rap eu tic re g im e n . O n th e

b asis o f th ese lim ited da ta , the answ er is

u nc erta in . A lth ou gh the n on spe cific re-

a ctiv ity to D N C B w as m ain ta ine d in fou r

p atien ts and even rev e rsed fro m n eg ativ eto p os it ive in 12 patients , it is no t c le ar

w h eth er B C G w a s respo ns ib le . C o nse -

q ue n tly w e ha ve b eg un a p ro spe ctive tria l

th at w ill ran do m ize pa tie n ts w ith a d -

v an ce d T 3 a nd T 4 les io ns in to a d ju va n t

c he m o the ra py a lon e v ersu s ch em oim m un o-

the ra py .

H op efu lly a c om bin at ion o f p rese n tly

a va ila b le tre a tm e n t m od a litie s -su rge ry ,

rad ia tion the rapy , chem oth e rapy , and im -

m u no th erapy-w ill re su lt in a m ore su c -

c e ssfu l m e an s fo r d isea se c on tro l in a

g rea te r p ercen tag e of th ese pa tien ts .

R E F E R E N C E S

I . E ilber FR , M o rton D L , K e tcham A S : C orre la -

tion o f im m uno lo g ic reac tiv ity and c lin ica l

co urse in pa tien ts w ith so lid neop la sm s o f th e

h ead and n eck in N eop la sia o fthe H ead an d N eck,

Proceed ings 17th A nnu a l C lin ica l C onfe rence

o n C ancer , M . D . A nd erson H o sp ita l and T u m o r

Institu te, C h icag o , Y ea r B ook M edica l P ub -

lishers ‘974 pp. 2 1 1 -21 9

2 . Y ou ng R C , C o rde r M P , H ay ne s H A , e t. a /.:

D elay ed hyp ersensitiv ity in H odgk in ’s d isease -

a s tud y o f 10 3 un trea ted pa tie n ts . A m 7 M ed

52:63-72 1972

3. E ilber F R , N izze JA , M o rton D L: S eq ue n tia l

ev alu atio n of gene ral im m une com pe ten ce in

cance r p a tien ts: co rrela tion w ith c lin ica l cou rse .

C ancer 35 :6 60 -66 5, 1975

4. E ilb e r FR , M orto n D L , K e tch am A S : Im m u no-

lo g ic abno rm a litie s in head and n eck cance r.

. .lm 7 S u r g 12 8 :534 -538 , 1974

5. R oth JA , E ilbe r F R , M orton D L : E ffec t o f

su rge ry on in v itro lym pho cy te fun ctio n . S u r g

Forum 25:102-104 1974

6 . H ersh E M : M o difica tion o f ho st de fense m ech a-

n ism s, in C ancer M ed icine , ed ited by H olland

JF , F re i E , P h ilade lph ia, L ea & F eb ige r, 1973 ,

p p 6 8 1-699

7. C o sim i A B , B run ste tter F H , K em m ere r W T ,

M iller B N : C e llu la r im m u ne com pe ten ce o f

bre a st c a nc er p at ien ts re c eiv ing rad io the rap y .

Arch Surg 107:531 535 ‘973

8. T h om a s JW , C o y P , L e w is H S , Y u e n A : E ffe ct

o f th erapeu tic irrad ia tio n on ly m ph ocy te tran s-

fo rm atio n in lun g cance r. C a n c e r 27 10 46-10 50,

1 9 7 1

9 . G hosse in N A , B o sw orth JL , B ases R E : T he

e ffect o f rad ica l rad io th erapy o n d elayed h ype r-

sensitiv ity and th e in flam m ato ry re sp onse.

Cancer 35:1616-1620 1975

10 . C l e m e n t JA , K ram er S : Im m un ocom pe ten ce in

pa tien ts w ith so lid tum o rs un de rg o ing co ba lt 6 0

irradiation. Cancer 34:193 -19 6, 197 4

I I. G ros s L , M anfred i O L , P ro tos A : E ffec t o f co -

ba lt 60 irra d ia tion up on c ell-m ed ia te d im mu n ity .

R ad io log y 1 06:65 3 -65 5 , 1973

1 2. M o rto n D L : C a n ce r im m un o th era py : an ov er-

v iew . Sem in O n co lo gy i 29 7 -3I0 , 19 74

13 . M o rto n D L , E ilb er F R , H olm es E C , H un t JS ,

K e tc ha m A S , S ilv ers te in M J, S pa rks F C : B C G



C H E M O IM M U N O T H E R A P Y IN H E A D A N D N E C K L E S IO N S 1087

im m un o the rap y of m e lanom a: su m m ary of

seven yea r exp erience. A n n S u rg 8o :635 -643 ,

‘974

14 . G utte rm an JU , M av lig it G , G o ttleib JA :

C h em oim m uno the rap y of d issem in ated m a lig -nan t m e lanom a w ith d im e thy l tria zen o im ida -

zo le ca rbo xo m ide (D T IC ) an d B a cillu s C a l-

m e tte -G uer in . N E ng l 7 M ed 2 91 5 92 -5 97 1 97 4

15 . D ona lds on R C : M eth o trex ate p lu s B ac i l lu s

Ca lme t te -Guer in (B C G ) an d iso n ia z id in th e

tre atm e n t o f ca nc er o f th e he ad a n d n ec k . ur n 7

S u r g 124:527-534 1972

i6 . D on a ld son R C : C hem oim m un otherapy fo r can-

cer o f the head and neck . A m 7 S u rg 126:507-

512 1973

17 . B leumink E , N a te r JP , K o ops H S , T ite T H : A

sta nda rd m e tho d for D N C B sensitiz a tion te stin gin pa tien ts w ith neop lasm s. C a n c e r 3 3 9I 1-9 15 ,

‘974

8. Je sse R H , L indb e rg R D : E ff icacy o f com b in ing

rad ia tion th e rapy w ith su rg ica l p ro cedu re s in

pat ien ts w ith ce rv ica l m e ta stas is from squ am ou s

ca n ce r o f th e o rop ha ryn x an d h yp op ha ryn x .

Cancer 35:1163-1166 97

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