The metastatic patterns of osteosarcoma

Br. J. Cancer (1975) 32, 87 THE METASTATIC PATTERNS OF OSTEOSARCOMA G. M. JEFFREE, C. H. G. PRICE AND H. A. SISSONS* Bone Tumour Registry, Bristol Royal Infirmary, Bristol BS2 8HW and the Bristol From the Royal National Orthopaedic Ho8pital*, 234 Great Portland Street, London WIN 6SD Received 3 February 1975. Accepted 14 March 1975 Summary.-The paper presents a detailed comparison of the anatomical distribution and frequency of clinically evident metastases in 152 cases of osteosarcoma, and autopsy findings in 43 cases. The behaviour of long bone tumours is contrasted with those arising elsewhere, which tend to metastasize less widely because of early death from effects of the primary tumour. In both clinical and autopsy series long bone tumours produced lung metastases (LM) in over 90% of patients dying with metastases, but the terminal frequency of extra-pulmonary metastases (EPM) rises from a clinical level of 33% to 83% at autopsy. There was little difference between tumours of the major long bones in the frequency of either LM or EPM, but EPM from the humerus tended to be fewer and sited above the diaphragm and from the femur below it. EPM most often involved other bones, notably vertebrae and pelvis. Not more than 10% of tumours invaded regional lymph nodes but terminally a quarter of the long bone tumours had metastasized to heart and abdomen. The infrequency of metastases in muscle was confirmed. The median time for LM was 5-6 months after starting treatment, for EPM 9-10. months. First metastases after 24 months were infrequent, especially in children. With delay in the appearance of metastases, whether LM or EPM, post-metastatic survival lengthened. Neither age, sex nor mode of treatment of the primary notably affected metastatic frequency, although recurrences were much more numerous when radiotherapy, even with high dosage, was the definitive treatment. Local recurrence usually appeared within 6-8 months and was shown to lead to increased frequency of osseous metastases. It is suggested that terminal dissemination may often be tertiary but not always from a pulmonary secondary. THE PAST 30 years' experience of the treatment of osteosarcoma shows universally bad results for any large series of cases. This is due both to the intrinsic limitations of current therapeutic methods and to concentration upon control or destruction of the primary tumour only, although it becomes increasingly obvious that the overwhelming lethal factor is distant metastatic growth, particularly in the lungs. With tumours of long bones, which comprise the great majority of osteosarcomata presenting in young people, lung secondaries are almost invariably the cause of death, even though metastases in other sites are not infrequent and are also potentially lethal. The explosion in diversity and scope of chemotherapy in the last decade is already producing better prognoses for some solid tumours. It is hoped that the use of cytotoxic drugs in the treatment of osteosarcoma may prolong the disease-free survival in this tumour also. Planned treatment along these lines requires a precise knowledge of tumour behaviour, especially of the dominating metastatic activity. We present an analytical study of the metastatic patterns of osteosarcoma arising in otherwise normal bones, as found both clinically G. M. JEFFREE, C. H. G. PRICE AND H. A. SISSONS 88 -,,Brain 3 Thyroid 3 Cervical nodes 3 Skull 3-Jaw & mastoid 3 -Shoulder muscle I _Thoracic nodes 7 127 FLUNGS nodes I _ -I rtebe 16 -Spleen Chestwall7 -Liver 5, Gall bladder y 2 Ce rvical vertebrae 2 Pe ctoral girdle 3 Sternum 2+ Humerus 3 Ribs 2 Do)rsal & lumbar --~~~~~Axillary rtebrae 16 L-A tf S- Pelvis 15 4 vei Sacrum 2 |lF %,! Adrenal 5 Kidney 4 Pancreas 3 Abdomen 13 < Mesenteric & peritoneal nodes 3 Subcutaneous 2 Iliac nodes 2 nodes I Thigh muscles 1 Tibia 1 Tarsus I\ 135 CASES. ll 40 Autopsies 95 Clinical records only FiG. 1 -Metastases to bone and soft tissue from osteosarcoma-all cases, THE METASTATIC PATTERNS OF OSTEOSARCOMA 89 and autopsy evidence. That this has some validity may be deduced from the very similar figures obtained in the 2 series for pulmonary metastases from the long bone PATIENTS AND METHODS tumours, and for death due to effects of Clinical evaluation of met astases (Fig. 2, the primary tumour in other sites. It cannot be assumed that they are entirely Tables I and VII) since some autopsies may have The records used for this study are comparable carried out on account of unusual essentially the same as for a previous paper been or unexpected death, which (Price and Jeffree, 1973), namely the clinical clinicalbefindings referable to metastases in obscure records and radiographs of 124 consecutive might sites. cases of osteosarcoma of long bones and 28 cases of osteosarcoma of other bones RESULTS registered with the Bristol Bone Tumour Lung metastases (LM) and extra-pulmonary Registry (BTR). The term " other bones " metastases (EPM) from osteosarcoma of is used for all primary sites but the long long bones bones of the limbs. Three cases-one long The clinical data are shown in Fig. 2 bone tumour and 2 of other bones-were not included in the previous study. As and 4 and Table I. a few patients have died or developed Of 124 patients, 91 (73%) had clinicmetastases over the past year, there may be ally evident metastases, 84 (68%) had some apparent discrepancies in the data. clinically evident LM and 30 (24%) had Though the recorded information may be clinically evident EPM. extremely meagre and clinical data are Both LM and EPM occurred in the therefore minimal, the authors have tried same case in 23 (19%), leaving 61 (49%) to get the fullest possible information on the progress of all patients and the times with LM only and 7 (5 %) with only of first clinical or radiographic evidence EPM. Of the 91 patients dying with metastases, 30 (33%) had evident EPM of all metastases. but the autopsy records (Table III) Metastases found at autopsy (Fig. 3, Tables show a frequency of EPM at death of III and VIII) 83%. Thus radical or palliative treatOnly 10 of the BTR patients came to ment for EPM will be required in 33-83% autopsy. One died from coronary artery of cases with metastases, approaching disease 12 years after high thigh amputation the higher figure sub-terminally. for a tumour of lower femur: no evidence Table I shows the anatomical disof tumour was found at autopsy. In the tribution of clinical metastases, and data other 9 cases-6 osteosarcomata of long from 29 autopsies are given in Table III. bones and 3 of other bones-the clinical evidence of metastases may be compared Table II summarizes the clinical incidence with the autopsy findings (Fig. 3). More of LM and EPM from tumours of different autopsy records were obtained by courtesy sites. The site of the primary tumour of a number of centres, most notably the does not materially affect the frequency Cancer Research Campaign Bone Tumour o (...truncated)