Solitary metastases in Carcinoma of the bronchus

Brit. o~. Dis. Chest Q969) 63, x5o.

Solitary Metastases in Carcinoma of the Bronchus THOMAS

J.

DEELEY

AND

DAPHNE

H. LINE

Departments of Radiotherapyand Mcdiclne (ChestClinic), Hammersmith Hospitaland Royal PostgraduateMedical School, London W I

C AR CI N O~tA of the bronchus is responsible for a considerable number of deaths each year. In 1966 the number of male deaths in England and Wales from this disease was 22,591 and the number of female deaths 4,404, accounting for 38.6~o of male deaths from cancer and 8.97 o of female deaths (Registrar General 1968). At present the treatment which seems to hold the best chance of a ' cure' is surgery. Only a relatively small proportion of patients, however, are suitable for radical operation aimed at curing the disease. Thompson (1967) found that in a series of 1,o7o patients admitted to hospital with a carcinoma of the bronchus 5o~o were unsuitable on clinical grounds, 2o~o were found to have an inoperable growth at bronchoscopy and a further IO~o were found to be inoperable at thoracotomy. Therefore only 2O~o are suitable for surgery. Some of the inoperable cases are suitable for a radical course of radiotherapy, but this can be given only where there is no evidence of spread of the disease outside the chest. In these inoperable cases a small proportion (6~o) have survived for 5 years after treatment (Deeley 1967; Deeley & Singh I967). The high incidence of metastases means that m a n y of the patients are suitable only for palliative radiotherapy at the most, and m a n y patients are not suitable for any treatment. The presence of metastases outside the chest has usually been taken to be an indication of widespread dissemination of the disease and a hopeless prognosis. It is possible, however, that in some of these patients a single distant metastasis may be the only manifestation of dissemination. I f this is so and the deposit can be satisfactorily ablated together with the primary growth in the chest, it m a y be possible to 'salvage' a few patients who previously have been considered to have a disease too advanced for radical treatment. This paper sets out to investigate the necropsy findings in a group of patients with a carcinoma of the bronchus, and to determine the incidence and distribution of solitary metastases outside the chest. The necropsies of patients referred either to the Chest Clinic or the Radiotherapy Department of this hospital have been reviewed. These have been carried out at various hospitals so that the group is heterogeneous in that it represents the histological interpretations of several pathologists. The histological sections have not been reexamined by one person, but it has been possible from the reports to divide (Receivedfor publication, September x968)

SOLITARY

METASTASES

IN C A R C I N O M A

OF THE

BRONCHUS

ISI

them all into 4 main groups--squamous, oat cell, anaplastic and adenocarcinoma. There are m a n y objections to the interpretation of results obtained at necropsy. The cases are selected from patients who have died in hospital and where necropsies have been performed, but the statistics obtained may not represent the true incidence of metastases. In addition, even at postmortem examination, it is not possible to obtain a complete picture of the metastatic pattern. The necropsy findings are gross; some structures may not have been examined and it would need serial sections to discover small loci of malignant disease. However, the information reported here provides us with the best available evidence of the disease in the body and is better than clinical data alone. For the purposes of this investigation only metastases outside the chest have been included. We define a metastasis as 'solitary' when it is the only one found outside the chest at necropsy.

Investigations This investigation is based on the findings of 647 necropsies in patients who died from bronchial carcinoma; in 5o2 (78~o) metastases were found outside the chest. The proportion of metastases varied with the histology of the primary t u m o u r (Table I). The proportion of solitary metastases at the main sites is shown in Table II. TABLE I.

METASTASES OUTSIDE THE CHEST

Histology Anaplastic

Squamous

Oat cell

038

i87

171

5i

I44 61

175 94

14o 82

43 84

No, of patients Metastases outside chest ~o

T A B L E II. SITE OF SOLITARY ~ X T R A T H O R A C I C

Site

Brain Vertebrae Other bones Liver Adrenals Kidneys Pancreas Stomach Eye Supraclavicular nodes Cervical nodes Total

Wo. with secondaries at site

Adenocarcinoma

METASTASES IN

Wo. where metastasis was solitary

lO9 160 94 o65 o 14 IOO 79 I8 2 87 78

22 6 6 °4 14 8 2 I I Io 3

--

97

647 PATIENTS

Percentage where metastasis was solitary

2o 4 7 9 7 8 3 6 -Ix 4

DEELEY AND LINE

I52

There were no solitary metastases at any of the other sites examined. The influence of the histology of the primary lesion is shown i n Table III. It will be seen that there is a higher proportion of solitary metastases with squamous lesions than with the other histological types. T A B L E III. P R O P O R T I O N OF SOLITARY I~ETASTASES ]FOR THE DIFFERENT HISTOLOGICAL TYPES OF TUMOUR

No. of cases with metastases outside chest No. of cases with solitary metastasis ~o

Squamous

Oat cell

Anaplastic

Adenocarcinoma

Total

I44

175

I4o

43

502

39 27

33 I9

I9 I4

6 14

97 19

Treatment The fact that a proportion of metastases from a carcinoma of the bronchus m a y be solitary suggests that radical treatment given to the primary lesion and to the metastasis m a y successfully cure the disease in a small number of cases. The treatment of cerebral metastases has been described by Deeley and RiceEdwards (I968). Almost half of the patients who completed a course of radiotherapy to the brain were able to return to a relatively normal life for at least one month, i 5 ~ o for more than 6 months and 7~o for more than one year. O f these patients 4~o survived for more than 3 years after the treatment to the brain. These results with cerebral metastases encouraged us to assess the results of radiotherapy to solitary metastases at other sites. The cases treated have fallen into 2 groups: (I) Where the patient presented with a primary tumour and a metastasis which was thought to be solitary. (2) Where a solitary metastasis arose in patients whose primary lesion was considered to be under control. In all cases a tumour dose of at least 3,000 reds in IO treatments in z4 days was given. In cases presenting with supraclavicular node involvement it would seem reasonable to treat the primary lesion in the neck, the mediastinum and the supraclavicular node area with one field in toto. This is possible with supervoltage radiotherapy. I f nodes develop in the supraclavicular fosse after radical treatment to the chest they are treated with a dircct X-ray field. The results of treatment are shown in Table IV. Sixteen patients with secondary deposits in the cervical nodes were given a radical course of radiotherapy to the chest and to the glands. One patient survived one year. If a bone lesion was thought to be solitary a radical course of radiotherapy was given. The majority of patients with bone secondaries, however, have widespread dissemination of the disease and only a palliative dose of radiation

SOLITARY METASTASES IN CARCINOMA OF T H E BRONCHUS

153

TABLE I V . SURVIVAL I~ATES PATIENTS TREATED FOR ~/IETASTASES IN SUPRACLAVICULAR NODES No. of cases I year years 3 years

4 years 5 years

7° 15 (20%) 5 (7%) 2 (307o)

I (I°7o) I (I7o)

is given to relieve symptoms. Thirty-five patients, with 'solitary' metastases, have received a radical course of radiotherapy; two survived one year. Discussion Metastases from lung carcinoma occur by lymphatic spread, by direct infiltration and by involvement of the blood vessels. I f cancer cells have only to penetrate the pulmonary veins to metastasize one would expect such metastases to become widespread and probably distributed evenly throughout the body. But this is not so. Fried (I 948) showed that the more remote the organ is from the primary site the smaller is the incidence of metastases to that organ. Greene (1957) was able to collect only a total of IO metastases to the phalanges and it has been shown that other remote organs such as the ovary are seldom the site of blood borne metastases (Karsh 195 i). It has also been suggested that there is a predilection for some organs to receive metastases (Russell 195o ). Coman (I953) suggested that the factors affecting the anatomical distribution of metastatic tumours were: (I) The lodgement of embolic turnout ceils. (2) The survival of the arrested embolic cells. (3) The establishment of a new blood supply and stroma. (4) Local environmental conditions favourable to the growth. The importance of the local environment had been pointed out by Paget in his 'soil hypothesis' as early as I889, It can be postulated that while widespread dissemination may occur, certain tissues either inhibit or do not encourage the growth of metastases. It is thus possible that a metastasis may be solitary because it was either the only embolic turnout cell that had lodged or the only cell that had survived or had established a suitable blood supply, or because there was no local environmental condition which prevented its growth. This investigation shows that a proportion of metastases outside the chest in carcinoma of the bronchus may be solitary at the time of necropsy. The incidence of solitary metastases is higher in squamous-celled lesions than in the other types of tumours. It is suggested that where the primary lesion is under control a secondary deposit should receive radical radiotherapy if there is no clinical evidence of spread to other organs. The results of treatment of brain secondaries show that subsequent survival m a y be worthwhile; also there are a small number of survivors after treatment ofsupraclavicular fossa metastases.

I54

DEELEY AND LINE

Our results with bone and cervical node secondaries have not been encouraging, but the numbers treated are small. We will continue to treat these because a small proportion were found to be solitary at necropsy. A deposit in the eye would also appear to merit radical treatment. Although solitary metastases may occur at other sites, they may not be amenable to treatment. The diagnosis of secondary deposits in the kidney, adrenals, pancreas and stomach is seldom made clinically. Small deposits are difficult to diagnose in the liver and treatment of this organ is difficult because of its poor tolerance to irradiation. Summary The necropsy reports of 647 patients with a proved carcinoma of the bronchus have been received to determine the incidence of solitary secondary deposits. It is shown that these are more likely to be found with squamous lesions of the other histological types. The fact that some deposits may be solitary calls for a more active approach to the treatment of these lesions, and doses of radiotherapy should be given at ablating the solitary metastasis rather than alleviating troublesome symptoms.

Acknowledgements We thank the many pathologists who have made the necropsy reports available to us and also Dr P. Stradling for his help.

References COMAN, D. R. (1953) Mechanisms responsible for the origin and distribution of blood-borne tumor metastases. Cancer Res., x3, 397. DEELEY, T . J . (1967) The treatment of carcinoma of the bronchus. Brit. 07. Radiol., 4o, 8oi. DEELEY, T . J . & RIcE-EDWARDS,J. M. ( 1968) Radiotherapy in the management of cerebral secondaries from bronchial carcinoma. Lancet, x, 12o9. DEELEY, T . J . & SINOH, S. P. (1967) Treatment of inoperable carcinoma of the bronchus by megavoltage X-rays. Thorax, 22, 562. FRIED, B. M. (I 948) Bronchogenic Carcinoma and Adenoma. London: Bailli~re. GREENE, M. H. (1957) Metastasis of pulmonary carcinoma to the phalanges of the hand. 07. Bone 07t Burg., 39A, 972KAI/SH, J. (1951) Secondary malignant disease of the ovaries. Amer. 07. Obstet. Gyncc., 6x, I54. PAGET, S. (1889) Distribution of secondary growths in cancer of the breast. Lancet, x, 571. REGISTRAR GENERAL (1968) Statistical Review for England & Wales for the year 1966. RUSSELL, D. S. (I95O) The pathology ofintracranial tumours. Postgrad. reed. 07, 26, 124. THOMPSON, D. T. (1967) Conservative resection in surgery for bronchogenic carcinoma. 07. thorac, cardiovasc. Burg., 53, I59-