Metastatic Spread of Osteosarcoma

Br. J. Cancer (1973) 28, 515 METASTATIC SPREAD OF OSTEOSARCOMA C. H. G. PRICE AND GRACE M. JEFFREE From the Bristol Bone Tumnour Registry and Pathology Research Laboratory, Phase I Building, Bristol Royal Infirmary, Brisol, BS2 8HWf Received 14 July 1973. Accepted 24 July 1973 Summary.-A study is presented of the rate of metastatic spread of osteosarcoma. The series consists of 123 tumours in long bones and 26 elsewhere in the skeleton. All tumours occurred in otherwise normal bones and were histologically proven. With a few stated exceptions all the cases were consecutively registered. Both the mean disease-free interval from the time of starting treatment and the crude survival curves are given. The long bone cases are analysed by groups according to the method of treatment, the patient's sex, age and tumour site. There were too few tumours of all other sites to warrant this discriminative treatment. Whilst the results of surgical treatment are better than for radiotherapy or a combined technique, the differences are not statistically significant and the information is recorded primarily to assist the evaluation of new forms of treatment of occult and overt metastases. Some problems in connection with such clinical trials are discussed briefly. THE appallingly high mortalitv of human osteosarcoma, which in the United Kingdom is still of the ultimate order of 85040, has largely been due to the inadequacy of any treatment for metastases. Were this not so, the cure rate could be dramatically increased to about 700o, which is equal to the proportion of these tumours arising in the long bones and which usuallv provide nearly threequarters of any series of cases. During the past decade the universally poor 5 year survival rates, which range from nil to 3000, have stimulated an active search for some means of restraining metastatic spread, e.g., by pre-operative ligation of the veins draining the tumour site (Kuehn, Tamoney and Gossling, 1970), by prophylactic irradiation of the lungs (Newton, 1973: Jenkin, 1973) or by immunotherapy (Marcove et al., 1973: Enneking and Marsh, 1973). A vigorous attack has also been launched upon overt pulmonary secondaries with chemotherapy bv Cortes et al. (1973), Rosen et al. (1973), Jaffe (1972) and other workers. Infusion of cvtotoxic drugs into the bronchial arteries has been reported by Ohno (1971) and multiple resections for presumed solitary secondaries have been carried out by Martini et al. (1971). This more aggressive attitude towards metastatic osteosarcoma, especially of lungs, has resulted in the situation that now in many centres relatively few patients-particularly juveniles-will be treated solely by surgery or radiotherapy. Thus the time is past for more precise determination of the rate of metastatic dissemination of tumours treated bv these two original and accepted techniques. Osteosarcoma is relatively uncommon. The annual incidence of this tumour, arising in otherwise normal bones, is estimated at between 2 and 3 tumours/106 population from the records of the Bristol Bone Tumour Registry, 1946-72 inclusive. Applying the 1971 census figure of a total population of 55 million in the United Kingdom, there are only about 130 new cases per annum in persons without other bone disease. Allowing for the possibility that 15°I of all local cases are missing n 516 C. H. G. PRICE A.N_D GRACE M. JEFFR E the Bristol registrations, the total number would not annuallv exceed 150 new cases. Thus it is difficult even for a major centre to set up anv strictlv controlled trial of these newer ancillary methods of treating the generalized disease (British Medical Journal, Editorial, 1971). It is highly desirable that there should be comparable data available in order to evaluate at the earliest time the benefit or otherwise of anv new methods of treating metastatic osteosarcoma. Some of the more promising advances in tumour chemotherapy, e.g. adriamycin, have serious and unpleasant side-effects which can only be justified by the overall benefit to the patient in terms of prolonged useful and enjoyable life. WVhilst some information is obtained from therapeutic trials in laboratory- animals, rodents and other small species do not readily produce either spontaneous or experimental osteosarcomata which equal the human tumour in their abilitv to metastasize. Moreover, at the present time in the treatment of the the human disease there are important considerations other than the simple duration of life after diagnesis and treatment. Undoubtedly the most valuable model svstem for experimental work is canine osteosarcoma (Owen, 1973), but this is not readilv available. Furthermore, the results of the effects of cvtotoxic drugs or immunotherapy upon tumours in tissue culture are even more difficult to interpret in terms of the human clinical situation. The results of treatment of osteosarcoma have been published bv many centres, but almost all in the form of crude survival curves or 3, 5 and 10 vear survival rates, without any indication of the presence or absence of active local or metastatic tumour. Some reports include patients with Paget's disease complicated bv osteosarcoma a form with an almost hopeless prognosis and extremely rapid metastatic spread (Price and Goldie, 1969). Other series mav be biased in their selection by the tvpe of institution where they are collected-e.g., from a children's hospital. Likewise, differences in race, religion or social custom may affect the time when patients seek medical aid for a swollen painful limb and such factors, together with personal experience, may influence the decision as to the method of treatment adopted, thus possiblv determining the ultimate result. The purpose therefore of this paper is to record metastatic behaviour of all cases of osteosarcoma arising in otherwise normal bones recorded bv the Bristol Bone Tumour Registrv during the vears 1946-72 inclusive. Patients of all ages and tumours of all sites are included but analysed in separate groups. Crude survival curves and estimates of the mean disease-free interval (DFI) are given for the following groups of cases: Series A-123 tumours of long bones. Series B-26 tumours of all other sites. Patients known to have Paget's disease and fibrous dysplasia were excluded, as were one patient with multicentric osteosarcoma, one with simultaneous osteosarcoma of femur and bronchial carcinoma, one patient whose tumour was treated by resection only and 2 who received no definitive treatment. MATERIALS A-ND METHODS The cases included in this study are consecutive registrations, all tumours being proven histologically. For each patient the following information has been obtained from the case notes and radiographs: 1. The nature of the treatment and date of amputation and/or commencement of radiotherapy. 2. The time when metastases have first been either clinically or radiographically evident. Where this has not been recorded, due to the absen (...truncated)