T H E T R E A T M E N T O F C A R C I N O M A ' O F T H E L A R Y N X B Y S U P E R V O L T A G E R A D I O T H E R A P Y

ROBERT MORRISON, M.D.(EDIN.), F.R.C.P.E., F.R.C.S.E., F.F.R. and T H O M A S J. DEELEY, M.B.(BIRM.), F.F.R., D.M.R.T.

Medical Research Council Radiotherapeutic Research Unit and Hammersmith Hospital, London, W. 12

LARYNGEAL cancer is one of the most satisfying new growths to treat. As most of the tumours arise on the vocal cord and cause hoarseness at an early stage they are usually detected when quite small in size. Because there are only a few small capillary lymphatic vessels in the vocal cord and the lymph drainage is poor, a spread of the tumour cells to the lymph nodes in the neck occurs infrequently. Dis- semination by the bloodstream is also rare. Success- ful local therapy either by surgery or by radiation, therefore, has a very good chance of curing the patient. This is confirmed by the published results f rom either form of treatment.

A high percentage of squamous carcinomata are sensitive to the ionising radiations used in therapy and the tumours can be destroyed completely if a sufficient dose is given. The anatomical position of the growth and the accuracy with which it can be localised make the technique of irradiation fairly simple. As only a small volume of normal tissue is treated, the general disturbance and the effect of the radiation on neighbouring organs is relatively slight. One considerable advantage of radiation treatment compared with the surgical removal of the growth is the better functional result. A patient who has cancer of this organ treated by radiotherapy frequently recovers completely f rom the hoarseness which is the common presenting symptom.

In the treatment of laryngeal cancer by radiation x-rays generated at 200 kV. and gamma rays have been used extensively. Some workers have ex- pressed a preference for gamma radiation because of the lesser skin reactions and they have also claimed better clinical results (Pohle 1950 and Allchin et al 1955). When supervoltage therapy came to be de- veloped for deep seated growths it seemed doubtful whether there would be any advantage in using this penetrating radiation for tumours as near the sur- face of the body as throat and laryngeai cancer. As far as was known there was no specific biological advantage in employing the shorter wave length radiations. The only possible advantage might be in a different physical distribution of the radiation. In the case of 8 MeV radiation the tissues between 1.3 and 2.1 cm. below the skin receive the peak dose and this is at approximately the depth of the vocal cord. Using a single field, therefore, applied over

the larynx the tumour receives the highest dose and there is a falling gradient of dose towards the normal tissues. This distribution of the radiation may be of some biological advantage. The design of this supervoltage apparatus is such that a more sharply defined beam is used which allows the tumour to be treated with the minimum of damage to the normal tissues near the growth.

Table 1 shows the integral doses received in the treatment of a lesion confined to the vocal cord by (1) a radium beam using three 5 cm. diameter fields; (2) 240 kV. x-rays using two opposing 5 cm. dia- meter fields, and (3) an 8 MeV linear accelerator using a single 5 cm. field. It will be seen that with the supervoltage radiation the integral dose is lower than with the other methods and considerably lower than with the radium beam unit.

TABLE 1 INTEGRAL DOSE PEg 1,000 RADS M.T.D.

Radium beam technique

0.675 Mgm. rads

240 kV. D.X.R.

0.214 Mgm. rads

8 MeV L.A.

0.167 Mgm. rads

T H E CLASSIFICATION OF LARYNGEAL CANCER

The original division of laryngeal cancer into intrinsic and extrinsic growths was convenient surgically, as it determined whether or not the growth was suitable for surgical treatment. When patients are treated by radiotherapy it is desirable to have a system of classification which takes account of the differences in behaviour of the tumours at the various anatomical sites and differ- ences in the extent of spread.

At Copenhagen in 1953 the International Committee for the stage-grouping of cancer suggested a method of classifica- tion based on the system describing the extent of the primary tumour (T), the condition of the regional lymph nodes (N) and the presence or absence of distant metastases (M). It was suggested that only tumours which fall within the limits of the endolarynx should be regarded as laryngeal growths, but there was some disagreement regarding the upper limit of the larynx.

As tumours which arise above and below the vocal cord behave differently from cordal tumours and have a different prognosis, it is advisable to place them in separate groups,

145

146 C L I N I C A L R A D I O L O G Y

The three groups recomnaended by the Committee were glottic tumours, supraglottic turnouts and subglottic turnouts. Similar sub-divisions were suggested previously by Baclesse (1949), Leborgne (1951) and Lederman (1952).

The T.N.M. staging of laryngeal turnouts suggested follows the general principles laid down by the Committee in the staging of cancer and also by the World Health Organisation. For laryngeal turnouts these a r e : -

P r i m a r y : - - T.1 Carcinoma is limited to the mucous membrane (full

mobility of the larynx is retained). T.2 The carcinoma infiltrates but does not extend beyond

the larynx (full mobility of larynx is impaired or lost). T.3 Carcinoma has extended beyond the larynx. No

involvement of the skin. T.4 Involvement of the skin.

N o d e s : - - N.a No palpable nodes. N.b Nodes palpable and movable. N.c Nodes fixed.

D i s t a n t m e t a s t a s e s : - - M. Distant metastases present. Because of the large number of separate groups (see Table

2) this classification is 0nly of practical value when large numbers of patients are treated. The Committee suggested four clinical stages.

Stage I Carcinoma is limited to the mucous membrane; no nodes. (T.1, N.a.)

Stage II There is evidence of infiltration as shown by fixity of the vocal cords; no nodes. (T.2, N.a.)

Stage III Extension of the growth beyond the larynx and/or palpable lymph nodes. (T.1, N.b, T.2, N.b, T.3, N.a, N.b.)

Stage IV Involvement of sldn and/or fixed nodes and/or distant metastases. (T.1, N.c, T.2, N.c, T.3, N.c, T.4, N.a, N.b, N.c or T.M.)

Classification in present series.--In the patients we have treated we have tried to follow the above method of staging. The upper limit of the larynx has been taken at the level of the hyoid bone as suggested by Lederman (1952). Tumours of the suprahyoid epiglottis, aryepiglottic folds and the arytenoids have, therefore, not been considered as cancers of the larynx and have not been included in this group of patients.

While the suggested T.N.M. classification is very well suited to cordal growths which constitute 82 per cent of the total in our series, it is not entirely satisfactory for growths which have arisen at the other sites, particularly in the supraglottic region. Fixation of the vocal cord may not be present even with large supraglottic tumours or may be difficult to observe because of the size of the growth. The numbers of supraglottic tumours are relatively few and it would seem satisfactory to group stages T. 1 and T.2 together. The same grouping could also be used for subglottic tumours.

If a large number of glottic turnouts are available for analysis it would be of advantage to divide the early turnouts into those which involve one cord

only, T.1 (a) and those which have spread to the adjacent mucosa of the larynx T. 1 (b) as these two groups have different survival rates (see Table 5). Tumours which have spread to involve the anterior commissure and the opposite vocal cord are in- cluded in the second group.

PATIENTS TREATED We are reporting the results of treatment in a

series of 103 patients who were treated between 1954 and 1960 by an 8 MeV linear accelerator. Our policy has been to treht all laryngeal cancers by radiotherapy in the first instance. When radio- therapy failed to destroy the growth completely a total laryngectomy was undertaken if the disease was still operable. Out of the 103 patients, twelve later had the radical operation performed. A b road

TABLE 2

T . N . M . CLASSIFICATION OF CASES

Supraglot t ic

Primary T. 1 T.2 T.3 I T.4

Total I

Glott ic

Primary T.I T.2 T.3 T.4

Total l

Subglot t ic i

Primary T.1 i T.2 T.3 T.4

i Total I

I Nodes

N.a l N.b

2 9 0

1 3 1

i - -

11 5

50 18 3

71

1 1

N.c

1 0 1

! 2

2 1 5 2 1 0

i 8 J

[ 1

I 1

i 3 I

I - I - I - -

Total

4 12 2

18

53 25

4

82

2 1

division of the 103 tumours showed that eighteen were supraglottic, eighty-two were glottic and three were subglottic. Table 2 shows an analysis accord- ing to the T.N.M. staging and Table 3 gives the recommended International staging of the cases.

TABLE 3

STAGING

Stage Supraglottic Glottic Subglottic T o t a l

I 2 50 1 53 II i 9 18 1 28 III ' 5 11 1 17 IV I 2 3 I - - 5

T R E A T M E N T O F C A R C I N O M A O F T H E L A R Y N X

TREATMENT T E C H N I Q U E The past experience of many clinicians has estab-

lished that an average dose of between 6,000 and 7,000 r gamma radiation given by daily treatments over six weeks is near the opt imum dose for squamous cell tumours at this site. The first patients treated at 8 MeV were given a dose of about the same biological effectiveness, viz., 5,800 rad units in six weeks. After treating a small group of patients at this dose level, it was noticed that the reactions which normally develop on the mucosa took longer to appear and were not so severe as was previously observed with gamma radiation. Be- cause of these observations, the tumour doses were increased and lesions which could be treated by a field of 25 sq.cm, or less were given a dose of 7,000 fads. For the more extensive growths when larger fields had to be used the dose was reduced to 6,400 rads.. These are the maximum doses given. They were not exceeded, even when a confluent mucosal reaction had not developed by the end of the course.

The extent of the tumour can be defined fairly accurately by laryngoscopy, soft tissue radiography and tomography. Check radiographs demon- Stnge No. of patients strated the extent of tissue being irradiated. The i- treated radiation was directed either f rom a single lateral s0 field for unilateral lesions (Fig. 1) or by two fields III 18 directly opposed where a spread had occurred to the I III 11 opposite side of the larynx. I ]v 3

While undergoing the course of treatment the patients rarely experienced any general constitu- tional upset apart f rom some tiredness and lassi- tude. Local reactions caused a temporary loss of voice and sometimes an irritable, unproductive c o u g h .

RESULTS OF T R E A T M E N T Figure 2 shows the yearly survival rates for the

whole group of patients. I t will be seen that after

% Survival

IC)C

9C

×5

FIG. I

Isodose distribution using a single field.

147

the third year.the chance of the patients dying from the disease is very small. This was noted also in a series of cases reported by Bond (1954) who found that the survival curve three years after treatment ran almost parallel to the normal survival curve for the whole population of the same age group and he suggested that a three-year survival rate should be a suitable criterion to measure the efficacy of the treatment.

Supraglottic tumours.--There were eighteen supra- glottic tumours. The site of origin of these was the posterior aspect of the epiglottis, the vestibule of the larynx, the false cord and the laryngeal ven- tricle. In the present series seven out of eighteen cases had node involvement. Because of the small numbers it is not possible to express the results according to stage but the three-year survival for all cases was 38 per cent.

TABLE 4 GLOTTIC TUMOURS. SURVIVAL RATES ACCORDING TO STAGE

Treated surgically after radiotherapy

3 5 0 0 }

3-year survival

(per cent)

76 66

53

Glottic tumours.--There were eighty-two patients with tumours of the glottis. The numbers in each stage and the three-year survival rate is shown in Table 4. In the group of Stage I cases there was a difference in survival according to whether the growth was confined to one cord or had spread beyond the cord to the anterior commissure or to

tYcar 2Years 3Years 4Years 5Years

il cl I I I I I I I I I I I I 1 I I I

4 8 12 16 2 0 2 4 2 8 3 2 3 6 4 0 4 4 4 8 5 2 5 6 60 Months

Fro. 2 Graph showing survival rates for 103 patients treated by

supervoltage therapy.

148

the ventricle or subglottic region. Table 5 shows the three-year survival in the two groups of cases.

TABLE 5 STAGE I GLOTTIC TUMOURS.

SURVIVAL ACCORDING TO EXTENT OF DISEASE

C L I N I C A L R A D I O L O G Y

'FABLE 6

RECURRENCES AFTER RADIOTHERAPY

Confined to Spread beyond cord-cord mobile cord-cord mobile

No of cases. 29 21

3-year survival 85 per cent 63 per cent

Stage I cases which have spread beyond the cord have a similar three-year survival rate to the Stage II cases and might be more appropriately grouped with them.

THE PLACE OF SURGERY

Of the twelve patients in whom a laryngeetomy was performed eight had glottic tumours and four had supraglottie tumours. Of the twelve, six are alive and without evidence of the disease and two of these have survived for more than three years. One further patient survived for three years and died of the disease. Careful and frequent follow-up after the radiation treatment is very important so that any recurrence can be detected early, when a laryngectomy may still be possible.

The operations did not appear to be made more difficult by the previous irradiation. This may be because the amount of irradiated tissue was quite small and most of it was removed at the operation. Because the skin at the affected site received only a fraction of the tumour dose and showed no radiation reaction no difficulty was experienced with the closure of the skin flaps.

ANALYSIS OF FAILURES IN R E L A T I O N TO DOSE

It was thought that a review of the cases in which radiotherapy had failed to cure the growth might prove instructive and suggest means by which the radiation technique might be improved. One of the important factors would appear to be the dose of radiation given. In the first group of patients treated, the mean tumour dose was 5,800 rads in six weeks. In a later group, the tumour dose was increased and small tumours in which the treatment fields were 25 sq,cm, or less in area were given a dose of 7,000 fads. For tumours requiring larger fields a dose of 6,400 rads was given. The incidence of recurrence of the tumour at the primary site at the two dose levels is shown in Table 6.

Glottic f tumours ~.

Supraglottie tumours

Mean Tumour Dose

5,760 rads in six weeks

Local No. recurrence treated

11 32 34~

6 7 86%

6,400-7,000 rads in six weeks

Local No. recur rence t rea ted

2 19 l l~

0 5 0%

The longest period before a first recurrence was noted was twenty-nine months from the time of treatment. To make the groups comparable only cases who could be followed up for at least three years have been included. It will be seen that in the glottic tumours the recurrence rate in the growths treated to the higher dose was significantly less than the rate at the lower dose level. A similar difference is seen in the supraglottic tumours; although the numbers are small they are significantly different.

It is possible that the dose level of 6,400 to 7,000 rads may still be too low. No serious complications of the treatment have been observed so far and probably higher doses could be given, especially to the small tumours, but further investigation is re- quired to decide on an optimum dose.

SUMMARY

The results of treating 103 patients with car- cinoma of the larynx by an 8 MeV linear accelerator are given. Methods of classifying tumours are discussed and some modifications in the Inter- national method of staging are suggested. The influence of the tumour dose on the survival rate is shown in the tables.

Acknowledgement.--We are grateful to Miss J. A. Stevenson, B.SC. for the calculations of the integral dose.

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British Practice in Radiotherapy, Ed. CARLINO, E. R., WIrqDEYrR, B. W., & S~TnERS, D. W. London: Butter- worth.

BACLESSE, F. (1949). Brit. 3". Radiol. Suppl. 3. BOND, W. H. (1954). Annual Cancer Report. Ed. AXNOTT,

W. M., & BROOKE, B. N. United Birmingham Hospitals. LrBOR~NE, F. E. (1951). J. Fae. Radiol. (Lond.), 3, 24. LEDERMAN, M. (1952). Brit. J. Radiol. 22, 462. POHLE, E. A. (1950). Clinical Radiation Therapy, 2nd ed.

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