VoL.
114,
No.
I
MALIGNANT
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ANALYSIS By CARLOS
OF A.
PEREZ, JOSEPH
TUMORS
FAILURES
AND
FACTORS
M.D., LAUREN V. H. OGURA, M.D., ST.
OF
UMEROUS reports have been pub lished on the treatment of carcinoma of the tonsil, either by a radical surgical resection2’7”4”7’27 or by radiation therapy.6’8”5’ 19,21-24,26,30 In the more recent past, a combined approach using preoperative irradiation and operation has been practiced at some institutions.’3”9’24 Five year cure rates have varied fiom 15 to 40 per cent. Although several publications have analyzed the curability of these lesions depending on clinical stage, only a few attempts have been made to systematically correlate the factors which may exist in the host or the tumor that will influence the results of treatment. Profound differences in pathologic classification are encountered in the literature22 and most of the reports deal with epithelial tumors, !ymphomas frequently being excluded. The present study attempts to correlate the various parameters with survival. The mechanisms of failure for treatment modalities were analyzed. The medical records, as well as the pathologic slides and reports of i. patients with various types of carcinoma and 25 patients with malignant lymphoma of the tonsil were reviewed in retrospect. The material comprises the experience in the treatment of carcinoma of the tonsil at the Mallinckrodt Institute of Radiology and Barnes Hospital Medical Center, Washington University School of Medicine, St. Louis, Missouri, from January, 1950 to December, 1967, all patients being available for a minimum 3 year follow-up and 132 for years. Included are a group of patients who received preoperative radiation therapy at our institution, Presented
at the
Fifty-third
Annual
Meeting
of the
M.D.,f WILLIAM B. E. POWERS, M.D.
MILL,
M.D.,
hut were operated upon at the Veterans Administration Hospital and St. Louis City Hospital by members of the Washington University Staff. Eight additional patients referred from other institutions for the treatment of recurrent tumors are not included, but 3 patients receiving incomplete irradiation and 4 patients in the preoperative group found to be inoperable are included. The results in the treatment of a significant portion of these patients have been published recently.’9 METHODS
As described tients
(2)
American
Radium
in
TREATMENT
that by
publication, different
the methods:
pa-
Radiation therapy alone. Irradiation was given to 6i patients with 5,ooo tads tumor dose (TD) in 6 weeks (orthovoltage-prior to 1959) or 6,ooo rads TD with cobalt 6o (after 1959). Usually the tonsillar fossa and adjacent tissues, as well as the entire neck were irradiated. Only a few cases with T, lesions were treated with an ipsilateral port and the lower necks were not irradiated in 4 patients. Preoperative irradiation. Forty-eight patients were treated by preoperative cobalt 6o irradiation to the primary tumor and the ipsilateral neck lymph nodes, usually to a dose of 2,000 or 3,000 rads, delivered at a rate of i,ooo rads per week. Patients with more advanced lesions on occasion received 4,000 to 5,000 rads preoperatively; 3-6 weeks after completion of the irradiation, a radical tonsillectomy, combined with a jawSociety,
Radiation Therapy, Mallinckrodt Institute of Radiology Washington University School of Medicine, St. Louis, Missouri. Address: Lester E. Cox Medical Center, Springfield, Missouri.
43
OF
treated
were (i)
From the Divisionsof Otolaryngology, § Present
PROGNOSIS
MISSOURI
N
*
TONSIL*
AFFECTING
ACKERMAN, and WILLIAM
LOUIS,
THE
Mexico, and
Surgical
D.F.,
Mexico, Pathologyj
March and
15-18,
the
1971.
Department
o
Perez,
44
Ackerman,
Mill,
neck
dissection was performed. Four initially admitted to this group were found to be inoperable at the completion of their therapy because of poor regression of massive oropharyngeai cancer or large fixed neck lymph nodes. Surgery. A radical tonsillectomy with resection of the contiguous tissues in the soft palate, lateral pharyngeal wall and base of tongue was performed in 19 patients, usually in combination with an ipsilateral neck dissection. Ri don implantation. A small group of i6 patients was treated by the Division of Plastic Suigery with radon implantation to the tonsillar fossa (10-20 one millicurie seeds) in the majority of the cases combined with an ipsilateral radical neck dis-
Ogura
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(.)
Powers
T2-Lesions
patients
(,)
and
JANUARY,
3-5
tension
to
T,-Lesions limited
with
cm., adjacent
larger extension
1972
minimal
ex-
structures
than 5 cm., to adjacent
with struc-
tures
T4-Massive
tumors
nasopharynx tongue,
geal
the to the base of the or lateral phaiyn-
extending
down epiglottis
from
wall
Metastatic
Lymph
Nodes
in the Neck
N0-No clinical lymph node Ni-Single, less than 3 cm. mobile lymph node N2-Single, mobile lymph than 3 cm. or multiple non-fixed lymph nodes N3-Large fixed, unilateral or bilateral lymphadenopathy ANALYSIS
OF
involvement in
diameter,
node larger ipsilateral lymph
node
RESULTS
section.
The
The were
patients treated
lymphoma
with malignant
to
doses
ranging
from
2,000
in the orthovoltage era and 3,500 to 4,003 rads after the installation of a cobalt 6o unit in 1959. In the earlier years, no attempt was made to treat the entire neck, but this has been routinely done in the past ia years. No prophylactic radiation of the mediastinum has been done. In patients with abdominal or other to 3,500
rads
manifestation therapy
of
has
been
tumor
spread,
combined
radiation
with
absolute 3 year cure rate with the methods of treatment was about 50 per cent and at 5 years ranged from 31 to4o per cent (Fig. i,zl and B). Six patients lost to follow-up are considered dead with tumor. All patients have been followed up until December, 1970 or until death. various
chemo-
therapy.
AGE
No striking difference was noted in the 5 year absolute cure rates when correlated with the age of the patients at the time of treatment. The table with these results was analyzed but not published for the sake of brevity.
CLASSIFICATION
Using the description the lymph nodes on the
of the tumor and hospital and radiation therapy records at the time of the initial examination, the patients with epi theli al tumors were retrospectively staged according to the following classification Primary
:15 Tumor
T,-Lesions localized less than 3 cm.
to in
the diameter
tonsil,
but
SEX
of the tonsil is predominant about 20 per cent of the cases in women. Although some authors have observed a better prognosis in this latter group,17’25’27 in our experience, the survival rates were comparable in both sex groups. In the preoperative irradiation group, there is a larger proportion of women surviving without tumor at 3 years, but on closer analysis 4 of them had early Carcinoma
in men, presenting
only
VOL.
114,
lesions
Malignant
No.
(T,,
T2),
which
carry
a better
Tumors
of the
prog-
45
Radiation 22/48
nosis. CLINICAL
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Tonsil
STAGE
Primary Tumor. Some differences in the various methods of treatment were noted in the cure of the tumor in relation to clinical staging. The results are not statistically significant because of the small number of patients treated in each group. However, all of the patients with T, lesions treated by irradiation alone, about 50 per cent of the ones with T,, and 35 per cent of those with T, lesions were cured. Except for the T, lesions, the results are comparable with the other methods of treatment (Fig. 2). All methods of treatment were equally ineffective in the treatment of massive T4 lesions, and only rarely was a patient cured. Metastatic Lymph Nodes. As has been reported in the past, patients with no clinical evidence of metastatic neck lymph nodes at the time of treatment had a very good prognosis. The 3 year cure rate was 75-80 per cent for the patients treated with irradiation alone or combined with a radical surgical procedure and o-6o per cent for those treated by surgical resection or radon implantation (Table I). The 3 year survival rate of patients with ipsilateral lymph nodes was about 40 per cent and comparable for all types of treatment. Patients with bilateral lymphadenopathy did very poorly, only I surviving after
MALES
(47%)
FEMALES
5/13 (3B%j
P3,
P-e-0
Pre-Op
Surgery
16/38
8/16
7/14
(42%)
(50%)
(50%)
7/10 (70%)
1/3
1/2
1
1
S’ep
4/12 330’
4/5 (5/0)
Totil
P:
// 23
,03/ /2
3fl /2S (30
Radon
L p:a
3/
4/12 (330)
MALES
FEMALES
42
30
20
12
B0 I. Carcinoma of the tonsil. Graphs showing (A) 3 and (B) 5 year absolute cure rates. Essentially the same cure rates were noted in men and women.
FIG.
irradiation. PATHOLOGIC HISTOLOGIC
FINDINGS CLASSIFICATION
All the pathologic slides reviewed and the patients (Table ii). The pathology of cancer concerned with squamous lymphomas. The diagnosis cell carcinoma following made without difficulty, instances of so-called thelioma.”
and reports were were reclassified of the tonsil is cell carcinoma or of squamous biopsy is usually except in the few “lymphoepi-
The microscopic pattern of squamous cell carcinoma can vary within a wide range (Fig. 3, ii and B; and C and D). Squamous cell carcinoma, both in the primary lesion and within the lymph node, can be sterilized by radiation therapy. At times, this results in large masses of keratin surrounded by giant cells (Fig. 4), or there can be replacement of the lymph node by fibrous tissue (Fig. 5). It is difficult to decide in
46
Perez, Ackerman, RADIATION
No
5/8
1-_.L 3/6
2/3
Ni
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Total
N2
-
1/3
13PRE-OPERATIVE
fl1TT2
-Tal
Ni
1/5*
1/74
&
Rx
-2JI16
N2
O/2
1/2
3/11
Il/lfl
N3
I
I03I_--1 0/3
13/40 0/2
Mi
Mi
t3.6
8/14 5/5
I
(100%)
lotal
3/7 Total
(4
(32
(27%)
3%)
SURGERY
12
RADON
13
No
1 /2
fli-14iotai
2/2
1972
6/10
13/19)
1-L43/11
I/I
N3
JANUARY,
12
ALONE
13
No
and Powers
Mill, Ogura
Ni
LffI
&jotl 4/6
1/4
0/2 1/6
N2
N2
1/2
0/2 0/1
N3
N3
0/1
6/16
Mi 0/6 2/4 4,9 Io
FIG.
2.
2/7
tol
of the tonsil. Five
Carcinoma
year
t Postoperative death in each group; # no autopsy; 0’ patient inoperable-incomplete (6,ooo rads). Eight additional patients treated
None
14/19
(%) Ipsilateral
*
Six
plete
t
patients
I/TO with
.
distant
Metastasis-
Surgery
8/io
6/32
(8o%)
(50%)
(45%) #{176}/4t metastasis;
Four One
NED=
patients inoperable; postoperative death no evidence of disease.
3 postoperative in each group.
Radon
4/6 (66%)
3/7
4/10
(43%)
(40%)
-
-
3 patients
therapy. deaths.
stage
with
various
treatment
modalities.
postoperative deaths; * patient died suddenly before therapy (3,ooo rads); &I patient inoperable-complete less than 5 years ago: 3 are alive, tumor free.
2
TONSIL
15/33
12/32
(37%) Bilateral
Preoperative Irradiationt
by clinical
had
incom-
surgery, therapy
instances whether the tumor is viable (Fig. 6). Difficulties occur in the diagnosis of malignant lymphoma because often there is an accompanying inflammatory reaction which masks the picture of lymphoma. In the cases of lymphoma, we have used the classification widely accepted as outlined by Rappaport.2#{176} Table ii shows that the 5 year cure was slightly better for those patients with keratinizing squamous cell carcinoma (,j per cent) than for non-keratinizing (30 per cent). The patients with well-differentiated lesions had a somewhat better prognosis (50 per cent), but no significant difference was noted when the tumor was moderately or poorly differentiated (about 35 per cent cure rates). many
OF THE
Clinically Palpable Lymph Node 3 Yr. Survival-NED
Radiation Therapy*
rates
I
TABLE CARCINOMA
cure
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VoL.
Malignant
No.
114,
Tumors
of the
Tonsil
47
Although “lymphoepithelioma” is common in the nasopharynx, where it carries a good prognosis, it is extremely unusual in the tonsillar area. Two out of 3 patients with this diagnosis survived years, which again may indicate a favorable host response to what is now known to be a nonkeratinizing squamous cell carcinoma. Most of the malignant lymphomas of the tonsil were classified as either lymphocytic or histiocytic
types
(former
lymphosarcoma
and The
reticulum
cell sarcoma,
prognosis
was
ent
for
2
iii).
Only
histologic variants (Table of Hodgkin’s disease was
OF
PATHOLOGIC
these i case
not
respectively).
significantly
differ-
observed. STATUS
SPECIMEN
The
3 and year survival rates were corwith the presence of “viable” tumor cells in the primary tumor or in the neck lymph nodes (Table iv). related
Radiation who had
(i)
.-
been
‘
..
‘I
Therapy.Fourteen
patients
with
treated
radical
FIG. 3. (C) Rare pattern be called transitional (D) Undifferentiated (35#{176}x).
..
-
,.
.
#{149}--
#{149}..-
4
surviving.
1*1
4-,
that could (iso x). carcinoma
irradiation were operated upon: in 3 instances because of residual ulceration in the tonsil; and in the remaining ii because of persistent induration in the neck, which was suspected by the otolaryngologist to be residual tumor. Of the 7 patients without viable tumor cells, 6 survhed for 3 years with no evidence of tumor and #{231} for 5 years. Two patients out of 3 with non-viable residual carcinoma in the neck lymph nodes survived. However, the presence of intact tumor cells in the tonsil or the lymph nodes carried a very poor prognosis, only i out of patients
A’ -.
of squamous cell cell carcinoma squamous cell
‘A
.?Sl1 FIG. 3. (A) Photomicrograph of heavily keratinized squamous cell carcinoma (300 x). (B) Nonkeratinizing squamous cell carcinoma with a pattern of so-called “lymphoepithelioma” (350 x).
(2)
Preoperative tients with
Irradiation. All 8 panegative specimens are surviving 3 and 5 years after treatment. Of those with no tumor in the tonsil, but positive lymph nodes, 2 out of 6 survived 3 years and none
48
Ackerman,
Perez,
Mill,
Ogura
and
Powers
JANUARY,
1972
tonsil
in the survival of the patients by this modality. About per cent of the patients with positive treated
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primary
tumor
lymph per
15
(,)
and
positive
nodes
survived 5 years.
cent
Surgery.
Radon
(4)
neck and
Implantation.
that the absence
it is noted
Again,
3 years
30
of
and negative neck lymph nodes in the specimen carries an excellent prognosis, most of the patients surviving (675 per cent). If there was evidence of residual tumor in the neck lymph nodes, 40 per cent of the patients survived 3 years and 20 per cent 5 recurrent
primary
tumor
years. NUMBER
OF
INVOLVED
OLOGIC
As
11G.
.
cinoma apy
(A) Undifferentiated squamous with very little keratinization, (350 x). (B) Following therapy,
large
masses
(150
x).
of
keratin
surrounded
cell
before there by
giant
car-
therare cells
out of , years. Of the patients with a positive primary tumor, but negative lymph nodes, out of 8 survived 3 years and 3 out of 7, 5 years. This suggests that the presence of positive lymph nodes is more significant than residual tumor in the
LYMPH
SI’ECIMEN
NODES AND
IN
THE
PATH-
PROGNOSIS
with no evidence of tumor in the neck lymph nodes at the time of radical neck dissections had a better outlook: 23 out of 32 patients survived 3 years (72 per cent) and i8 out of 29 survived years (62 per cent). Patients with a single positive lymph node also had a good prognosis, io out of 17 surviving 3 years and 5 years (59 per cent?). In contrast, only 8 out of 24 patients with 2 to 4 positive lymph nodes survived for 3 years (33 per cent) and only 2 out of 21 for 5 years ( per cent). Patients with more than 5 positive lymph nodes had an equally unfavorable prognosis, 4 out of 14 (28 per cent) being alive at 3 years and none out of patients
13
patients
expected,
5 years
at
(Tables
v
and
vi).
I-:
H’
--
-
6. After radiation therapy, keratinization is noted in an undifferentiated squamous cell carcinoma. There are masses of tumor cells which
11G.
11G.
5. Cervical
fibrous
tissue.
serially
sectioning
lymph No
node tumor
the
lymph
partially was node
replaced
found
(
after x).
by sub-
are
probably
ment
can
not
be made
viable,
(iso X).
but
no
definite
state-
VOL.
114,
Malignant
No.
Tumors
of the
CARCINOMA
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Radiation Therapy Alone
.
Squamous
Cell
Classification
Carcinoma
Keratinizing Well differentiated
3/3
49
II
TABLE
Histologic
Tonsil
OF THE TONSIL and
5 Year
Preoperative . Irradiation
Absolute
Cure
Surgery
.
Total
Radon
‘/3
2/4
Rates
c/
6/Il (54%)
Intermediate
6/15
6/23
4/8
3/5
6/14
i/
3/5
2/5
19/51 (37%)
Poorlydifferentiated undifferentiated
and
10/28
(%)
Non-Keratinizing Well differentiated
I/I i/6
Intermediate
5/’,
6/i6
9/3!
15/32
2/2
35/90
(%)
I/I
-
-
0/2
o/i
3/IT (30%)
Poorly differentiated undifferentiated
and
4/13
1/3
1/5
6/21 (27%)
4/8
5/19
0/2
1/4
!0/33
o/z
oh
Unspecified “Lymphoepithelioma” Undifferentiated
2/2
Transitional
i/i
o/z
Total
23/57
6/39
13/40
It
is worthwhile to point out that the of the patients with 2-4 positive lymph nodes surviving are in the group treated by combined preoperative irradiation and surgery. As was indicated in a previous publication,’9 this treatment modality has been characterized by a prolongation of tumor-free life span, which is confirmed by the significant number of patients surviving 3 years who died of their tumor by the fifth year. OF
0/4 i/i
majority
CAUSE
2/3
o/z
0/3
(30%)
DEATH
It is apparent that most deaths are due to uncontrolled tumor (about 30-40 per cent of all patients; Table vii). The probability of failure at various anatomic areas is analyzed in detail below. Since a significant proportion of the patients are in an advanced age, it is not uncommon to find intercurrent disease as a cause of death, particularly after several
years
of
6/,6
48/132
life. As was reported a greater proportion of complinoted in those patients treated
tumor-free
previously, cations was
III
TABLE LYMPHOMA
Histologic
Type
Lymphocytic Well differentiated Intermediate Poorly differentiated Hystiocytic Well differentiated Intermediate Poorly differentiated Hodgkin’s Total
disease
OF THE
TONSIL
5 Year Cure Rate
2/4
1/3 2/7
5/14
(%)
4/Jo
(40%)
I/I 1/5 2/4
0/i 9/25
(36%)
Perez,
50
Mill,
Ackerman,
Ogura
CARCINOMA
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OF
THE
Primary*_Neg.
Lymph
Nodes
Neg. Primary-Pos. Lymph Pos. Primary-Neg. Lymph Pos.Primary-Pos.LymphNodes Neck Dissection Not Done
Nodes Nodes
Total No
*
t
clinical
evidence
of tumor
with
by preoperative irradiation which is probably related trauma previously
The is
7 patients
in tonsil;
Non-viable tumor in 2 patients. Three patients inoperable, treated
of
the range with
viously
of
patients
5 Yr.
6/7*
5/7*
8/8
6/6
2/3t
2/3t
2/6
o/5
0/2
0/2
/8
3/7
4/6
1/2
0/2
7/21
3/18
4/10
18/47
16/43
I/
i/4
27/61
23/57
23/48
radical other
many
some
years
ago,
patients the records
were were
No. of Positive Lymph Nodes
Radiation Therapy
neck
Positive Neck Specimen Correlated Preoperative . Irradiationt
6/7
0
Yr.
3/6
3/4
3/4
2/To
4/9
2/9
i/
1/3
i/
i/
9/19
6/19
8/i6
6/16
residual
neck
lymph
nodes.
operation.
ANALYSIS
OF
In our previous report,19 recurrence in approximately of the patients developed
treated incom-
of
*
before
suspected
3 Yr.
pre-
and
TABLE
V
OF
THE
CARCINOMA
Number
for
Yr.
and no known cause of death could be ascertained in 9 patients. Practically all the patients with a malignant lymphoma who died, had generalized spread of their disease (Table viii).
tumors.’#{176}’1’
Because
died
13/40
3 Yr.
Radon
plete;
cancers
head
dissection
patient
surgery,’9
reported
having
neck
to the added procedure in
that
Surgery
.
3 Yr.
alone;
a radical surgical irradiated tissues. incidence of second primary
within
Preoperative . Irradiation
5 Yr.
had
Lymph With
FAILURES
it was 20-30
in
noted per
the
TONSIL
Radon
3/6
3/4
Total 23/32 (72%)
3/6
3/5
2/4
10/17
(59%) 2-4
0/4
3/5
5/12
0/3
8/24
(33%) or More
i/i
3/TO
0/I
0/2
4/14
(28%) *
Radical
t One
neck
patient Non-viable
dissection had neck tumor.
for
residual
dissection
mass done
after
previously
radiation
therapy.
for carcinoma
of pyriform
sinus.
that cent
tonsillar
Nodes in Initial Pathologic 3 Year Cure Rates
Surgery
.
11/15
2/2
1972
at Initial Treatment Cure Rates
3 Yr.
irradiation
and
JANUARY,
TONSIL
of Pathologic Specimen 3 and 5 Year Absolute Radiation Therapy Alone
Neg.
Powers
IV
TABLE
Status
and
VOL.
No.
114,
Malignant
I
Tumors
of the
TABLE CARCINOMA
Tonsil
51
VI
OF THE TONSIL
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Number of Positive Neck Lymph Nodes in Initial Pathologic Specimen Correlated with Year Absolute Cure Rates No. of Positive Lymph Nodes
Radiation Therapy *
Preoperative . . Irradiationt
s/’
0
Surgery
Radon
2/6
3/4
8/12
Total
18/29 (62%)
I
3/6
2/2
3/5
2/4
10/17
(59%) 2-4
0/4
1/9
1/5
0/3
2/21
(9%) or More *
t
Neck
o/i
dissection
One patient Non-viable
for residual had neck tumor.
0/9 mass
dissection
after
radiation
done
o/i
for carcinoma
of pyriform
area, with or without evidence of neck lymph node involvement or distant metastasis. Marginal failures were more common in the patients treated with preoperative irradiation (i per cent). Approximately
Cause
Tumor
VII
Disease
Second Primary Esophagus Lung Nasopharynx Colon
following
One patient dead Jaw-neck dissection
Pts.= patients.
TONSIL
(Unlimited
Time)
Preoperative
Therapy Pts.)
.
Surgery (19 Pts.)
.
(16 Pts.) 6
17
3
2
0
2 *
2t
I
I
I
i
i
(3rd Yr.) (6th Yr.) I (64 Yr.)
2
i
I
2
2
(i and
2
I
Yr.) I
I
surgical
removal
after cryotherapy for persistent
of tonsillar for tonsillar neck lymph
recurrence,
10
years
recurrence. node and necrotic
3
2
after
treatment.
ulcer
in pharynx
I month
P
6
21
3
Lymh
Radon
Tumor
Unknown #{149} Death
of Death
10
Complications Postoperative pneumonia Carotid rupture Postoperative cerebrovascular accident Cardiac arrest
t
OF THE
31
Intercurrent
sinus.
i per cent of the patients showed lymph node metastasis in the neck without either local or marginal failures. In the present analysis, we attempted to correlate the stage of the disease and the
TABLE CARCINOMA
(6i
0/13
therapy.
previously
Radiation
0/2
after
treatment.
Pelez,
52
LYMPHOMA
Sites
Mill,
VIII
TABLE
MALIGNANT
Ackerman,
of
OF
THE
Ogura
irradiation
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and No.
Total No. Failing -i6
of Patients-25
Tonsil
irradiation
few ease.
44
II
#{231}
20 20
6
Other
24
8 7 3 3
marginal
28
group
12
extension
12
4
I
4
Bone Marrow
4
16
Bone Metastasis
3
12
Unknown
2
counted
8
as i in every
location.
of failure according to the methods of treatment. This was done by tabulating the number of patients failing and each failure site was counted as i, so that a patient with local recurrence and positive neck lymph nodes would be represented in both groups. This way, the probability of a patient failing at a given site was determined (Fig. 7; and 8). With T, tumors, no failures were seen in patients treated by irradiation. Recurrences were noted in 3 out of 8 treated with mechanism different
preoperative
irradiation 40
per
cent
surgery alone or Most of the failures were either in the
ipsilateral With
and of
those
combined in the tonsillar
surgery
and
with latter fossa
in
with radon.
treated
2 groups or in the
neck lymph nodes. T2 lesions, the rate of failure
was
local
common
reported failures were
due
the 29
per
patients)
the
(about
majority treated by per
(23
(21
per
prognosis,
is in the incidence
of
cent).
only
a
disrange of 6 of distant their
cent.
previously,’9 some in the irradiation to
cent)
preoperative the marginal
control
failure
or higher, being
various in the
tumor
a poor
having
The
32
1
failure
more
have
patients
As
Viscera Spleen Liver Lung Brain Stomach Adrenal
about
were
per cent metastasis
recurrent
1972
group. a large pro-
It is noted that in the patients alone were local to those in the group in which
T4 lesions
Mediastinal
Each
opposed
failures
Lymph Nodes Retroperitoneal Neck
*
showed
cent). failures
irradiation
4
I
were local the preoperative with T3 lesions,
in
patients
6o per of the as
(
group
portion
Per Cent of Patients Failing at Each Site
No. of Failures
cent in the of the failures
per
Most
marginal
In
JANUARY,
35
approximately groups treated.
TONSIL
Failure*
Total
Poweis
and
of
nasophaiyngeal
the alone
tumor
which was not adequately covered by the radiation fields. The probability of failing in the ipsilateral neck lymph nodes is the same for the irradiation alone and the preoperative irradiation groups (i and i6 per cent, respectively) , but contralateral lymph node involvement was slightly more frequent in the preoperative irradiation group (12.5 per cent), where no treatment had been given. A large, but comparable proportion of patients died with distant metastasis in these 2 groups (19 per cent in the irradiation alone group and 21 per cent in the preoperative
The nant
irradiation
group).
the patients with maliglymphoma failed with known or strongly suspected retroperitoneal lymph nodes (. per cent) or with involvement of the liver, the spleen or both (Table yIn). Invariably, all the patients failing had generalized manifestations of the disease. However, the incidence of recurrence in the tonsil or in the neck lymph nodes was relatively low. Mediastinal spread was known in only 5 patients (20 per cent). Similar observations have been reported by Terz and Farr.28 In the past 5 years lymphangiograms as part
majority
of
have of
the
been
initial
obtained
routinely
work-up
in
an
ef-
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Vo,..
‘i,
Malignant
No.
Tumors
Radiation Pre-Op
23
Surgery
the Tonsil
TOTAL
NO.
PATI ENTS _______________ NuM3ER
15 (65%)
-
1
3
3
(13%)
1
2
2
FAI
-
6
5
4
(21%)
(16%)
(17%)
4
ENTS
2 MARGINAL
-_
2
(12%)
4
(16%)
IPSILATERAL
3 (12%) (21%)
NODES
‘LATERAL
NECK
(8%
2
(23%)
2
NODES
_____________
(20%)
inoperable committed 1 month after
2
_____________
NECK
2 patients .1 patient suicide
13 (76%)
8
(21%)
-
17
LING
LICAL
(24%)
2 -.-__
PATI
(60%)
4
53
______________Radiation
25
Radon
-
of
.
DISTANT
/TASTASIS OPPOSITE
operatio
FIG. 7. Carcinoma of the tonsil. Sites of failures by clinical stage of tumor with various treatment modalities (multiple failures counted as one in each location). Notice the excellent local control with radiation therapy alone in T, and T, lesions. In contrast, a high incidence of local failure is noted in T, and T4 lesions.
fort to better determine the extent of the disease. Because of the small number of patients, no conclusions can be drawn from these findings yet. DISCUSSION
Few reports are available in the literature analyzing the factors influencing the prognosis in carcinoma of the tonsil. However, fragmentary analysis of some of these is
encountered in the multiple papers with treatment results. In the present series, the age patients at the time of diagnosis and ment did not significantly influence over-all survival rates. Similar results been published by other authors.25 experience, the sex of the patients significantly affect the cure rate. et al.2’ reported a 5 year survival
dealing of the treatthe have In our did not Tapley rate
of
Perez,
54
Ackerman,
Mill,
Ogura oftime. of the
JANUARY,
1972
In our experience about 6o per cent recurrences appeared within i year
and
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Powers
and
8o
per
cent
between
2-3
years
after
treatment. Terz and Farr2T reported on 536 patients with carcinoma of the tonsillar area. After excluding i 14 for a variety ofreasons, the year survival for 303 patients treated with orthovoltage
with per
irradiation
was
tumor
control
a primary cent. In
treated
the
group
by surgical
rate
was
per
26
55 per
cent. In Stage cent with irradiation
per
*2
patients
in
to follow-up have died
lost
each
presumed with tumor
to
per
cent,
rate
of
resection, cent,
19.5
of
i86
42.9
patients
the
#{231} year
cure
with a local control i the cure rate was and
58
per
of 5i
cent
with surgery, Stage ii, 24 per cent, and 36 per cent and in Stage iii, 20 per cent with irradiation and 30 per cent with surgery. Calamel and Hoffmeister7 reported 53.1 per cent 5 year cure with surgical resection (29 patients) in contrast to 13.4 per cent with irradiation alone (5 patients). The
FIG. 8. Carcinoma of the tonsil. Total incidence of failures. Sites of failure in entire group of patients with carcinoma, according to treatment modalities. Notice the higher local failure rate with radiation therapy alone, as opposed to a higher number of marginal failures in the patients treated by preoperative irradiation and operation.
although excess higher
77 per cent in a group of 17 women treated, of whom 13 had been followed for 5 years. This was contrasted with the 21 per cent cure rate in a group of 64 men treated, of whom 52 had been followed for years. Terz and Farr27 found a better survival rate for women (37.8 per cent) than men
cent in the T1 group and 28 per cent in the T4 group. The absolute 5 year survival rate was 45.6 per cent for 57 patients with T,-T2 lesions, and 6 per cent for the 5 patients with T3-T4 tumors. Fletcher and Lindberg,’#{176} in 89 patients
technique
of
it
irradiation
is
and
with
tients, having
Lampe9
been
contrast
to
reported
per
72
cent
brought
38.7
carcinoma
ofthe
with
radical
irradiation
reports
out
cent)
in
a large
group
of
patients
at Memorial has been
on
comparable
or
superior
results
with radical irradiation have appeared in the literature.6’ 8-10,15,19.2123,25,26,30 Several reports indicating the adequacy of suigical resection for these lesions2’4”4 have follow-ups of i year, on the basis that most recurrences appear within this period
performed
on
T1 and under
pa-
102
T2 lesions control,
in
per
with
per
described,
mentioned
Hospital in New York. made of the effectiveness of various treatment modalities. Although some authors have advocated surgical resection as the treatment of choice for carcinoma of the tonsil,24’7’14’17’27 numerous
(24
treated Claim
not
that “doses in of 5,000 rads TD and frequently than 6,ooo rads TD were given.”
Fayos
is
tonsillar
fossa
alone
in 4 for local
or neck
treated
(operation lymph
node
surviving 2 years (48 per cent). In the patients treated with megavoltage 29 out of 66 survived 3 years recurrences)
(43.9
reported
43
per cent absolute of 52 for 5 years
cure rate). Scanlon irradiation,
et al.22 either
(36.5
cure per
rate), cent
and absolute
19
treated 131 patients by with continuous or split
course. The year survival rate was 72 per cent for Stage i, 6 per cent for Stage II, 54 per cent for Stage III and 22 per cent
VOL.
114,
for Stage viva! rate
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23 patients
tion per
Malignant
No.
Tumors
with an over-all year surper cent. A small group of treated with split course irradiai ,#{231} surviving at years (6
Iv,
of
52
showed cent). Most of the tumors of the tonsil have been classified as epidermoid carcinoma with different degrees of differentiation, or as undifferentiated tumors.21’22 A small number of transitional cell carcinomas or lymphoepitheliomas have been reported. Scanlon et al. observed no significant correlation between the pathologic nature of the primary tumor and the cure rate. Their survival rates, in the range of o per cent, are somewhat better than those in our series (39 per cent 5 year cure rate for keratinizing carcinoma and 30 per cent for non-keratinizing). In some ofthe reports in which the site of failure has been carefully identified, a significant proportion oflocal or marginal failures has been noted.’9’2’ Rider2’ found the highest incidence of recurrence in the base of the tongue (,j per cent of232 cases) compared with 13 per cent failures in the tonsil or pillars, 14 per cent in the neck lymph nodes and 14 per cent with distant metastasis. The year survival rate in patients with tumor confined to the tonsillar area was 31 per cent as opposed to 19 per cent in those with added involvement of the base of the tongue. His belief that failure to control tumor spread into the tongue is the most common cause of failure in treatment of cancer of the tonsillar area has not been substantiated in our series, in which only about 10 per cent failed in this particular anatomic site. In contrast, in 20 per cent of 89 patients with tonsillar fossa tumors, Fletcher and Lindberg’#{176} reported i8 primary local or marginal failures, of which 8 were in the tonsillar fossa, 4 in the base of the tongue and the remainder in the palate, posterior pillar, floor of the mouth and adjacent tissues. In 17 patients there was recurrence in the neck lymph nodes (i per cent); 8 patients were known to have died with distant metastasis.
of the
Tonsil
55
In general, the over-all incidence of metastatic neck lymph nodes is in the range of 60-70 per cent, 15 per cent of the patients presenting with bilateral lymphadenopathy.19 The presence of cervical lymph nodes at the time of treatment invariably has been found to affect the prognosis unfavorably, except for the series reported by Tapley et al.25 In our experience, the surviva! rate was closely correlated with the incidence of lymph node metastasis. Patients without lymph node metastasis had survival rates in the range of 70-80 per cent. With ipsilateral positive lymph nodes, the 3 year survival rate was about 40 per cent and only I patient with bilateral lymphadenopathy was cured. Similar results were reported by Scanlon et al.22 with survival rates in the range of 40-50 per cent in patients with ipsilateral positive neck lymph nodes and 10 per cent with contralateral or bilateral lymphadenopathy. The level of lymph node metastasis did not significantly influence the prognosis as long as they remained ipsilateral. Although some surgical series raise the question of the effectiveness of irradiation in controlling metastatic tumor in the lymph nodes of the neck,2 a growing body of evidence shows that this can be satisfactorily accomplished.’0”2’2’ In a group of 89 patients with carcinoma of the tonsillar fossa reported by Fletcher and Lindberg,’#{176} ‘7 failed in the neck ( of them combined with primary recurrence), and Rider2’ reported about i per cent neck lymph node recurrences. These failure rates are comparable to those in the present series. In our patients the site of failures has varied somewhat, depending on the various methods of treatment used. In the irradiation alone group, failures have been more common in the local area (19 patients, 3! per cent), whereas marginal failures were less frequent (6 patients, 10 per cent). The reverse is true for the patients treated with preoperative irradiation and operation, 6 out 0148 (i 2.5 per cent) failing locally and JO in the marginal tissues (2! per cent). Local failures were quite common in the
Perez, Ackerman, patients implantation
The
incidence node
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lymph ing
by surgery alone or radon per cent). of ipsilateral metastatic
treated
recurrence
per
14.8
(
cent
radiation
with
preoperative patients). Slightly per
(25
cent)
treated by implantation
patients
( 19
per
noted
in
the
patients 01
commonly
by
seen
irradiation
halfofthem
alone
were
examination, be treated with larger lymph
is present the
of
in patients at the initial
in the
lower
neck,
neck
of
with
for
the the
5,000
nodes
equally
satisfactory
with high combination
In
are
dose
in
results
radiation of moderate
followed a jaw-neck large
present
in the
by
a
can
radiation.29
the
radical
large neck,
or with of irradia-
a
tonsillectomy
dissection.
lesions
tieated
The
theoretically of a resistant
addition eliminate tumor.
irradiation,
remains high, the presence of sensitivity to of
a
resection
this possible However, the
The
Judicious
However,
the
residual
primary
site
particularly
therapy,
was In
found
our
was negative the cure rate
after to
series,
(tonsil was in the
or
in
radical
aggravate when and range
the lymph of 8o
but in
decreased when carcinoma the specimen. Although not significant (P.o), the prog-
was more unfavorable when the nodes contained viable tumor.
neck
It is important to emphasize that after radical irradiation, residual neck lymph nodes should be carefully evaluated for unequivocal evidence of tumor growth when a surgical procedure is contemplated. A
significant
shows by
of the regresprerequisite is are to be ex-
tonsil.
results.
nodes,
cent, found
nosis lymph
with
be obtained
therapy doses
this incidence of local failure and this is probably due to hypoxic cells with decreased would foci1s
nodes
after elective irradiation given (maximum) dose. T3 tumors, particularly if
With lymph
tion with
lymph
necks rads
predetermined
irradiation.
the
in
prognosis.27
specimen nodes),
rads
of metastatic
lower
the
radiation
statistically
5,coo
of
lymph
incidence
of
value
resection of a persistent primary or a radical neck dissection in the of a residual mass may contribute either
per was
doses
marginal The
a
preoperative
carcinoma
surgical lesion presence
TD should be carried out. This subject has been extensively reviewed by Million et al.18 and later by Berger et al.,’ who observed a very low to
of
higher incidence of complications, some of them fatal, may significantly offset the theoretic benefit of this combined approach. From the analysis of these patients, it is concluded that until proven otherwise, radiation therapy remains the best treatment
tumor,
nodes
the
combina-
volume of tissue to be initiation of radiation emphasized.’9 The sur-
remove
to improve
elective
lymph
sion
pected
only the upper necks should in small T, lesions. However, tumors, or if a positive neck
node
irradiation
node metastasis lymph nodes
incidence
of tissue, regardless the tumor. This if better results
paramount
present
the time of the initial treatment. Although the number of patients is not adequate for statistical analysis, it appears that radiation therapy alone (6,5oo-7,ooo rads TD) offers the greatest probability ofcure in patients with early lesions. In our experience, all T1 and 6o per cent of the T2 lesions were successfully treated by irradiation. Because of the extremely low mciof lymph palpable
should
of
of this
appreciably.
of “tatooing” the resected prior to therapy has been
amount in
the
and pro-
regression
purpose
increasing
1972
of irradiation, in the surgical
of partial the
therapy,
geon
radon
Distant
at
dence without
defeat
failures
more
but
because
tumor, tion
treated
cent),
cedure
out
resection alone neck dissection.
were
be-
JANUARY,
of moderate doses times a compromise
at
alone
were
radical and
metastases
the
is comparable,
use
of6i patients) with and i6 per cent irradiation (8 out of 48 higher neck failure rates
therapy
and Powers
Mill, Ogura
proportion
fibrosis
and
no viable tumor. lary gland with confused Although
with
of keratin
Occasionally, extensive a neck
a surgical
cure some patients practice has been insttution because
the
specimens
formation,
but
a submaxilfibrosis may be
lymph resection
node. alone
with early tumors, discontinued at of complications
can
this our and
Voi.
Malignant
No.
114,
Tumors
of the
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better alternative methods of treatment. Likewise, radon implantation has not been performed for at least 8 years.
Tonsil REFERENCES
1.
L. V., and DEL REGATO, J. A. Cancer: Diagnosis, Treatment and Prognosis. Fourth edition. C. V. Mosby Company, St.
ACKERMAN,
Louis, SUMMARY
The nosis
various in 169
factors patients
of the tonsil have cal stage of the presence
affecting with
are
the
lymph
most
prog.. tumors
been reviewed. primary tumor
of metastatic
neck
the
malignant
The cliniand the
nodes
important
in
the
prognostic
Age of the patient) sex and histologic classification of the tumor did not affect the prognosis. Patients with small primary tumors or no evidence ofmetastatic neck lymph nodes exhibited cure rates in the range of 70-80 per cent, in contrast to about 40 per cent factors.
for patients clinically
with palpable
more advanced lymph nodes.
of viable tumor in the tonsil lymph nodes of the surgical cated
a good
with
more
the
neck
prognosis, tion
positive
2
The
of
given
methods
most
of
the
However, lymph the
of failures of
patients nodes
carried dose
neck mdi-
treatment
radiation
of
Although
comparable
over-all
FAYOS,
cure
G. H., and mous cell carcinomas palatine arch. AM. THERAPY & NUCLEAR
FLETCHER,
II.
FLETCHER,
12.
HANKS,
13.
HENSCHKE,
reviewed, being
J. V., and LAMPE, I. Radiation of carcinoma of tonsillar region. ROENTGENOL., RAD. THERAPY & MED., 1971, III, 85-94.
10.
vanlocal
therapy AM. NUCLEAR
J.
LINDBERG, R. D. Squaof tonsillar area and J. ROENTGENOL., RAD. MED., 1966, 96, 574-
587.
rates
various methods of therapy alone, to doses of 6,oo to 7,000 rads, remains the best treatment for carcinoma of the tonsil. A higher incidence of complications was observed in patients treated by preoperative irradiation and operation. The importance of judicious post-treatment follow-up of these patients and of careful evaluation before performing radical surgery after high dose radiation therapy is stressed.
Carlos A. Perez, M.D. Mallinckrodt Institute of Radiology 510 South Kingshighway St. Louis, Missouri 63110
9.
1970.
G. W., and HEMMENWAY, W. G. Carciof tonsil: surgical treatment. LaryngoI 960, 70, 246-257. 3. R. R., and WEINER, S. Clinical manageof tonsillar carcinoma. Surg., Gynec. & 1965, 121, 1035-1038. 4. J. F. Cancer of retromolar area. I1.M.I1. Arch. Otolaryng., 1959, 69, 19-30. 5. BERGER, D. S., FLETCHER, G. H., LINDBERG, R. D., and JESSE, R. H., JR. Elective irradiation of neck lymphatics for squamous cell carcinomas of nasopharynx and oropharynx. AM. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1971, III, 66-72. 6. BERVEN, E. G. Malignant tumors of tonsil. zicta radio!., 1931, Suppl. i I. 7. CALAMEL, P. M., and HOFFMEISTER, F. S. Carcinoma of tonsil: comparison of surgical and radiation therapy. Am. 7. Surg., 1967, “1 582-586. 8. DALY, J. F., and FRIEDMAN, M. Carcinoma of tonsil. Laryngoscope, 1960, 70, 595-615.
radia-
those in the preoperative irradiation surgery groups being marginal.
were observed with treatment, radiation
ALLEN, noma scope, BAKER, ment Obst., BARBOSA,
a poor
for the are
failures
2.
in
preoperatively.
mechanisms
Ous
or in the specimen
specimen
regardless
therapy
and and
prognosis.
than dissection
lesions or Absence
57
G. H., and MACCOMB, tion Therapy in Management the Oral Cavity and Oropharynx. Thomas, Publisher, Springfield,
W. S. Radiaof Cancers of Charles C Ill., 1962, pp.
249-262.
G. E., BAGSHAW, M. A., and KAPLAN, H. S. Management of cervical lymph node metastasis by megavoltage radiotherapy. AM. J. ROENTGENOL., RAD. THERAPY & NuCLEAR MED., 1969, 105, 74-8 2. E. L., HILARI5, B. S., H. R., and STRONG, E. W. Value of preoperative x-ray therapy as adjunct to radical neck dissection. Radiology, 1966, 86, 450-453. NICKSON,
U. K., FRAZELL,
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04.
KLOPP, C. T., and SCHURTER, ment of cancer of soft Cancer, 1956, 9, 1239-1243.
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MACCOMB, W. S., and FLETCHER, G. H. Cancer of the Head and Neck. Williams & Wilkins Company, Baltimore, 1967, pp. 179-212. MARTIN, H. Case for prophylactic neck dissection. Cancer, 1951, , 92-97.
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M. Surgical palate and
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Perez,
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H. E., and SUGARBAKER, E. L. Cancer of tonsil. Am. 7. Surg., 1941,52, 158-196. i8. MILLION, R. R., FLETCHER, G. H., and J .SSE, R. H., JR. Evaluation of elective irradiation of neck for squamous cell carcinoma of nasopharynx, tonsillar fossa and base of tongue. Radiology, 1963, 8o, 973-988. 19. PEREZ, C. A., MILL, W. B., OGURA, J. H., and POWERS, W. E. Carcinoma of tonsil: sequential comparison of four treatment modalities. Radiology, 1970, 94, 649-659. 20. RAPPAPORT, H. Tumors of hematopoietic system. In: Atlas of Tumor Pathology. Section III, Fascicle 8. Armed Forces Institute of Pathology, 1966. 20. RIDER, W. D. Epithelial cancer of tonsillar area. Radiology, 1962, 78, 754-760. 22. SCANLON, P. W., DEVINE, K. D., WOOLNER, L. B.,andMCBEAN,J. B. Cancer of tonsil: 131 patients treated in II year period 1950 through 17.
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AM.
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STAPLE,
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THOMLINSON,
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Powers
N. DuV., EVANS, R. A., KLIGERMAN, M. N., and JACOX, H. W. Carcinoma of tonsillar area: factors influencing results of treatment. AM. J. ROENTGENOL., RAD. THERAPY & NuCLEAR MED., 1959, 82, 626-633.
25.
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D. Tonsil and palatine by radiotherapy.
and
POWERS, W. E. Carcinoma oftonsil: radiation therapy and consideration bined radiation and surgical Missouri Med., 1965, 62, 909-91 I.
MARTIN,
& 23.
Ogura
162-168.
J. H.,
and SCHULZ, M. D. Carcinoma review of treatment and its results of ninety cases. Radiology, 1947, 49,