EVALUATION OF RADIOGRAPHY AND ISOTOPIC SCINTIGRAPHY FOR DETECTING SKELETAL METASTASES IN BREAST CANCER

237

patients with tumours 5 cm or less in diameter (T1-2N0-1M0) may have scintigraphic evidence of metastases but normal results by radiology.3589A similar experience has led us to consider the proposition that skeletal scintigraphy should replace radiographic skeletal survey as the first method of screening for bone metastases in patients presenting with breast cancer. To this end we have analysed experience in Cardiff with technetium-phosphate scintigraphy. of

Hospital Practice EVALUATION OF RADIOGRAPHY AND ISOTOPIC SCINTIGRAPHY FOR

DETECTING SKELETAL METASTASES IN BREAST CANCER

J. G. ROBERTS* I. H. GRAVELLE M. BAUM

A. S. BLIGH K. G. LEACH L. E. HUGHES

Departments of Surgery, Diagnostic Radiology, and Medical Physics, Welsh National School of Medicine and University Hospital of Wales, Cardiff

Experience with technetium-phosphate compounds for skeletal scintigraphy in with breast cancer was analysed. When patients tumours were 5 cm or less in diameter (T1-2N0-1M0) metastases were demonstrated by radiographs in 1·7% (2/114). However, when radiography did not demonstrate metastases, lesions were found by scintigraphy in 41·3% (19/46). When lesions demonstrated by scintigraphy at the same site as abnormalities regarded as "benign" by radiography were excluded, 23% (11/46) had scintigraphs strongly suggestive of metastases. It is proposed that routine radiographic skeletal survey for patients presenting with breast cancer be abandoned, and replaced by skeletal scintigraphy, chest radiography, and specific localised radiographs of lesions demonstrated by scintigraphy. It is suggested that with this policy the development of expertise in interpreting scintigraphs will be accelerated, the cost of pre-treatment assessment will be reduced, and clinical management rationalised. Summary

PATIENTS

A

retrospective survey was carried out of skeletal radiology in 114 patients with clinically operable breast cancer with tumours 5 cm or less in diameter (Tl-2No-iMo). In a prospective study skeletal radiology and scintigraphy were carried out on 103 patients presenting with early and advanced breast cancer. 88 patients did not have radiographically demonstrable metastases and 15 had disseminated disease demonstrated by radiography (table i). TABLE

I—103

PATIENTS STUDIED IN PROSPECTIVE SURVEY

,

a

’Without radiographic metastases; only 78 scintigraphs analysed because quality was poor in 10.

Metastases

seen on

radiology.

In both studies investigations were carried out soon after the patient presented with breast cancer. Cancer was diagnosed by tissue histology in all cases and quoted tumour sizes are based on calliper measurements taken by a consultant surgeon when the patient was first seen in the breast clinic. METHODS

Skeletal

Radiology Radiographic skeletal survey included a chest radiograph,

INTRODUCTION

THE preoperative detection of metastases is important in primary breast cancer since if the disease is disseminated most surgeons will not carry out mastectomy even though the cancer may be technically operable. Skeletal radiology for metastases has well known limitations,l2 and metastases already present at mastectomy but not detected by this method probably account for many patients returning later with overt metastases. Some of these "occult" metastases can be demonstrated by skeletal scintigraphy.3 4 However, even with the newer and perhaps more specific radiopharmaceutical agents there is a reluctance on the part of many clinicians to base therapy on scintigraphy alone. This is in part due to the frequency of "false positive" abnormalities with this technique, probably due to "benign" bone disease.5 6 This has meant that both radiography and scintigraphy are undertaken in centres evaluating scintigraphy thus increasing the number and cost of investigations carried out on each patient. In studies where skeletal scintigraphy and radiography have been compared, many patients have more lesions on scintigraphy than on radiography.7 8 Furthermore, several studies have shown that 16-40% *Present address: Maelor Hospital, Wrexham, Clwyd, Wales

lateral view of the skull, anterior and lateral views of the dorsal and lumbar spine, and an anterior radiograph of the pelvis including the femoral heads. In the prospective series all radiographic skeletal surveys were reported or reviewed by two radiologists (A.S.B. and I.H.G.). The radiographic surveys in these patients were placed in one of three categories: (a) those within normal limits; (b) those demonstrating abnormalities due to "benign" disease; (c) those demonstrating metastases.

a

Skeletal

Scintigraphy Scintigraphy was carried out in the first ten weeks after initial presentation. The radiopharmaceutical agents used were technetium diphosphonate (Proctor and Gamble), or technetium polyphosphate (Diagnostic Isotopes). After intravenous injection of 10 mCi of the radiopharmaceutical agents, skeletal images were recorded using a gamma camera incorporating a 15 000-hole high-sensitivity 140 KEV collimator (Nuclear Chicago Pho Gamma III). After the patient had emptied her bladder, separate images were recorded of the paraxial skeleton, individual scapulae including the upper humeral shaft, and each half of the pelvis, including the upper part of the femur on that side. accumulated for the scintigraphs of the In views which are symmetrical about the midline, difficulties may be caused by anatomical features such as scoliosis or by the inclusion of different degrees of bladder activity. This was avoided by accumulating counts

200 000 counts

were

paraxial skeleton.

238 the second side for the time taken to the first side. on

acquire 200 000 for

Interpretation of Scintigraphs All scintigraphs were reported by A.S.B. and both investigations were reviewed by a surgeon and a radiologist (J.G.R. and A.S.B.). Scintigraphs were placed in three categories. A "good" scintigraph showed individual ribs, vertebrae, and scapulae clearly. The scintigraph was labelled "fair" when these structures were seen but there was some blurring and overlap especially in the vertebral column. In a "poor" scintigraph a featureless image of the skeleton was presented without recognisable definition of these structures. Areas of increased uptake in relation to the thyroid gland and rib ends were recognised as normal anatomical features.6 Since the skeleton

possible became

Localised breast

cancer

without

metastases on

radio-

graphy.-78 of 88 patients in this group had good or fair scintigraphs, and the results of these patients are shown in table ill, which summarises the radiographic and scintigraphic patterns observed together with TABLE III—COMPARISON OF SCINTIGRAPHY AND RADIOGRAPHY IN LOCALISED BREAST CANCER WITHOUT METASTASES ON RADIOGRAPHS

(PROSPECTIVE SERIES) -

assessed in one session it was not whether areas of increased uptake "hotter" with time (metastases) or

was

to comment on

relatively

"colder" with time (benign disease).6

RESULTS

Skeletal radiography in "early" breast cancer in retrospective survey.-The retrospective survey of skeletal radiographs involved 114 patients with cancers 5 cm or less in diameter. Only 2 patients in this survey had definite metastases on radiographs (1-7%). Metastases were suspected in a further 2 patients but were not confirmed by repeat radiographs nine and twelve months later. Skeletal scintigraphy and radiography in prospective study quality of scintigraphs.-Table m shows the quality of scintigraphs obtained in the 103 patients in this TABLE

II-QUALITY

OF SCINTIGRAPHS OBTAINED USING TWO

TECHNETIUM COMPOUNDS

..

.

,_.

those features denoting positive and negative sdndgraphs. Positive scintigraphs were found in 22 9% (11/46) of patients with tumours 5 cm or less and in 37-5% (12 of 32) patients with larger tumours. In 10 i of these 23 patients overt metastases have already developed (7 of these patients had tumours greater than ’ 5 cm) while metastases have developed in only 2 of 55 patients with negative scintigraphs. DISCUSSION

D.F.

=

2,&khgr;2

=

0-5707;

p

=

not

significant.

study. The small difference observed in scintigraphic quality between the two radiopharmaceutical agents used was not significant. Because of the lack of anatomical detail we feel that meaningful comments cannot be made about a poor scintigraph. Therefore, in the analysis which follows, patients with poor scintigraphs have been excluded. The poor-quality image seems to be related to the individual patients rather than faulty technique. On five occasions when the first scintigraph was poor it was repeated and four poor scintigraphs and one fair one were obtained. In practice if a scintigraph is poor, metastases should be sought in this patient by conventional skeletal radiography or by biochemical indices of dissemination.lo-14 and radiography in disseminated disease.-Bone metastases were demonstrated in 12 patients both by scintigraphy and radiography, but in 8 of these more lesions were seen on the scintigraphs than in the radiographs. Lesions were seen on scintigraphs in 2 of the 3 patients with metastases in the lungs on a chest X-ray who had normal skeletal

Comparison of scintigraphy

radiographs.

Our experience confirms that lesions will be found on scintigraphs in patients with radiographic evidence of bone metastases.3 8 The importance of a chest radiograph is demonstrated by the 3 patients with pulmonary metastases. While assessing a radiopharmaceutical agent which was different from those used in the present study we also saw a solitary radiographic metastasis which was not included in the gamma-camera field although other lesions were seen on the scintigraph. This disadvantage could however be avoided by a whole-body scanning technique. Radiographic evidence of disseminated disease would however, have been demonstrated in all patients by chest X-ray, skeletal scintigraphy, and specific localised radiographs of areas which were "hot" on scinrigraphy. Used in this way, scintigraphy would therefore be an appropriate first investigation in patients presenting with metastatic bone disease.

Clinically "Early" Breast Cancer The small number of metastases seen on radiography in patients with "early" breast cancer (2/114 strongly supports the argument for abandoning ske1eti radiography in these patients. This argument is reinforced by our experience with scintigraphy in patients with early breast cancer, when it is realised that t1:! .

239 most advanced scintigraphic techniques fail to demonstrate many metastases less than 2 cm in diameter, it is

probable that other patients in our series have bone metastases that have not been demonstrated. It is clear that conventional radiography can only reveal a small proportion of such metastases, and even in centres where scintigraphy is not available biochemical indices of bone metastases may be more appropriateio-14 than radiography. False-positive scintigraphs cannot be completely eliminated, but the majority of such scintigraphs are probably found in patients with a benign radiographic abnormality at the same site. If the sequence of investigation in our series had been chest X-ray, skeletal scintigraphy, and localised specific radiography these patients would all have been detected. Abnormalities would have been found on scintigraphy in 45% (35/78) of patients and these would have been subjected to specific localised radiography, so avoiding skeletal radiology in approximately 50% of patients. The clinician relies on radiological expertise to interpret equivocal skeletal radiographs based on criteria developed over many years of reporting metastases. If such a high degree of expertise is to be developed for skeletal scintigraphy, clinicians must request the examination, and the criteria indicating metastases must be refined. Our proposition is that the use of scintigraphy, chest X-ray, and localised specific radiographs of lesions shown by scintigraphy would accelerate the development of expertise in interpreting scintigraphs. Until the evaluation of alternative therapies15has been carried out on a wider scale, there is no strong argument for abandoning mastectomy in operable disease where skeletal scintigraphy is abnormal. Furthermore, by the time long-term results of adjuvant therapy are available the frequency of both falsepositive and false-negative scintigraphs may have been reduced by increasing expertise, more specific radiopharmaceutical agents, and techniques incorporating innovations such as whole-body imaging. This work was carried out while one of us (J.G.R.) was in receipt of a research fellowship from the Cancer Research Campaign. Requests for reprints should be addressed to L.E.H., University Department of Surgery, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN. REFERENCES 1. Bachman, A. 2. Edelstyn, G.

L., Sproul, E. E. Bull. N.Y. Acad. Med. 1955, 31, 146. A., Gillespie, P. J., Grebbell, F. S. Clin. Radiol. 1967,

18, 158. 3. Galasko, C. S. B. Br. J. Surg. 1969, 56, 757. 4. Galasko, C. S. B. ibid. 1975, 62, 694. 5. Sklaroff, D. M, Charles, N. D. Surgery Gynec. Obstet. 1968, 127, 763. 6. Merrick, M. V. Br. J. Radiol. 1975, 48, 327. 7. Galasko, C. S. B., Westerman, B.L1. J., Sellwood, R. A., Burn, J. I.

Br. J. Surg. 1968, 55, 613. 8. Citrin, D. L., Bessent, R. G., Blumgart, L. H., Greig, W. R. Proc. R. Soc. Med. 1975, 68, 386. 9. Hodman, H. C., Marty, R. Am. J. Surg. 1972, 124, 194. 10. Cuschieri, A. Br. J. Surg. 1973, 60, 800. 11. Cuschieri, A. Clin. Oncol. 1975, 1, 127. 12. Citrin, D. L., Cuschieri, A., Furnival, C., Blumgart, L. H. ibid. p.174. 13. Roberts, J. G., Williams, M., Henk, J. M., Bligh, A. S., Baum, M. ibid. p. 33. 14. Roberts, J. G., Keyser, J. W.. Baum, M. Br. J. Surg. 1975, 62, 816. 15. Fisher, B., Carbonne, P., Economou, S. G., Frelick, R., Glass, A., Lerner, H., Redmond, C., Zelen, M., Band, P., Katrych, D. L., Wolmark, N., Fisher, E. R. New Engl.J. Med. 1975, 292, 117.

Points of View THE MONEY MOTIVE* do

DOCTORS, on the whole, are conscientious folk; most of them not harbour dreams of great wealth, and though their bar-

gaining before 1948 was individual between person and person it was generally restrained-a modified market economy in fact. After 1948, however, the position changed completely, and it was the collective body of the doctors which negotiated with the Government-and still does. The economist would describe the present situation in medicine as being the result of a conflict between a force which is nearly a monopoly (the doctors) and something which is nearly the sole employer, that is a monopsony (the Department of Health). The State is a monopsonist because it is (with a few exceptions) the sole purchaser of the services of the doctors. Efforts to rid hospitals of private practice can be seen as one way of strengthening the hand of the monopsonist by making it more nearly completely the sole purchaser of services. Another way, now widely canvassed, is to restrict the rights of the doctors to leave the country to obtain posts in more affluent areas-for example, by making them repay to the State part of the cost of their education. These things should be opposed, however, not because of money, but because they violate a fundamental civil freedom.

relationship between monopsonist and monopolist is essentially one of conflict, and no-one is quite sure how or where this sort of conflict ends. Though we remember the confrontation with the miners in 1973, there is not, as yet, sufficient material to provide us with rules. The miners were able, by force, to raise their position in the table of wage-earners. But what makes the table in the first place? Why are doctors so high? We can see some clues here and there. Firstly, there is a sort of historic league table. Doctors have probably occupied the middle to upper ground for a very long time, and society (ours at least) doesn’t usually make abrupt changes in this sort of thing. Secondly, doctors have, compared with many members of the community, a very long training. Thirdly, doctors apparently have to be of high intelligence. Lastly, there is a proximity of the doctor in society which many other groups lack. The family doctor comes to the house, and the junior hospital doctor is seen to be hard-working and conscientious. The university teacher, on the other hand, is much more remote: though he may be more intelligent, work harder, and in the long-run be more influential, to the community he seems to lack immediate and obvious importance. The

Our nation is clearly on the decline: the standard of living is going down, and this process is likely to continue and even get worse for some time. Particularly in this sort of situation does it seem to be quite wrong for doctors to use their power to enforce a higher rate of pay, as did the miners. In any case, our two previous confrontations with the State, in 1911 and 1948, suggest that we will lose. For here our strength becomes our weakness: our proximity to our patients may make them think highly of us, but it also makes us think highly of them. It is difficult deliberately to ignore someone in such close proximity merely to obtain one’s own way. All this seems, in my mind, to be part of a fundamental are still, in 1975, dealing with Mrs Smith the widow, even if she has become obscured in the less immediately winsome appearance of Mrs Castle, the politician. We are forced to remember that, though in a sense a profession’s primary motivation must be to earn money, in another sense a professional man should think of his client’s interest as his

dilemma. We

*Based

on a paper read at a symposium on Money Greygarth Hall, Manchester, on Nov. 8, 1975.

and Medicine,