OSTEOSARCOMA IN A STUDY C. H. G. PRICE, H. G. WILLERT, BRISTOL, FRANKFURT, z. A study present aetiological The PRAGUE, is presented and K. ZHUBER, M. MATJOVSK’, in children English ENGLAND, GERMANY, six fifteen European M. IMMENKAMP, 125 CASES of age. treatment of treatment These cenfres. cases There 9 per after cent MuNIch, in a group have been is a slight feature is the very high proportion of tumours two and a half and five year disease-free survival a further metastasis W. KEYL, and VIENNA, P. GROH, MUNSTER-WESTFALEN, and results years M. SALZER, SALZER-KUNTSCHIK, CZECHOSLOVAKIA, of the aetiology under OF CHILDREN of 125 proven from osteosarcomas the preponderance, records but two of one the striking of the long bones of the limbs (96 per cent). rates were respectively 15 and 12 per cent, still living, but under observation for less than two and a half years. and a half years is very unusual, but no child with a tumour of an axial this length of time. Although the differences in the results valid, the largest number of long survivors GERMANY, GERMANY collected male AUSTRIA, HAMBURG, with Evidence of or girdle bone lived the lowest rate of local tumour recurrences. rates 1972). for clinical trials Although and behaves there Whether or by therapy there age are which at onset (Price few reports this aggressive 1966; are amputation in the figures for cases results these collected two available of the methods world amputation ( 19 1 of 903 patients) cent (I 19 of 501 without operation. of is between two 1974). by with after and This and a rate three cases figure excludes of 238 per with or per tumour: annual in the incidence million population tumours related Dr C. H. G. Price, F.R.C.Path. Research Fellow in Pathology, Royal Infirmary, Bristol, BS2 8HW, England. Dr K. Zhuber hk . Wiener Knochengeschwulstregister, Dr M Sal7er Professor M. P. Z. W. VOL. sc I H. G. Willert, The have Trifaud radiotherapy is not a common United Kingdom the the No. 3, AUGUST Spitalgasse 4, Osterreich. lnterdisziplin#{228}re Arbeitsgemeinschaft 1975 ablation is age group difficult. The is derived tumours were a study of bone or treatment any other centre is able, to collect records of a sufficiently to be adequate for detailed analysis. under review, this problem present series of 125 childhood from seven centres (Table I). histologically proven. of the aetiology and to information AND concerning the seven contributing These, together with sections, were This results paper of treatment. children were were under knowledge sarcomas METHODS patients was centres on detailed the radiographs examined ensuring agreement any doubtful cases, in Vienna on diagnosis. 125 examples accepted for in children so of and in Bristol, All age. To the largest far from thus After elimination of osteosarcoma evaluation. fifteen years this represents entered questionnaires. and histological reported. the of in children the best of our series of osteoNo histological grading of tumours was carried out ; nor was any distinction made between osteoblastic, chondroblastic, fibroblastic, anaplastic or other variants of osteosarcoma. University of Bristol, Pathologisch-Anatomisches Knochentumoren Immenkamp, Orthop#{228}dische Universit#{228}ts Klinik, M#{252}nster-Westfalen, Groh, Orthop#{228}dische Universit#{228}ts Klinik, Homburg, Saar, BRD. Mat#{235}jovsk, Erste Orthopadische Universit#{228}ts Klinik, Prag, CSSR. Keyl, Orthop#{228}dische Universit#{228}ts Klinik, M#{252}nchen, BRD. 57-B, disease no single PATIENTS by selective free of active Comparative at all ages immediate survival rate of 21 per cent compared patients) Osteosarcoma south-west a restricted of radio- of treatment literature prompt in adjuvant treatment. support for immediate amputa- method about six months then shown to be are still deplorable. for osteosarcoma gave a five years’ Meary Dr Dr Dr Dr All tumour by immediate Hospital different from (1972): treated Westminster at time, ofcases is even more osteosarcomas presents patients Thus With that prognosis Paget’s dysplasia. evidence influence in followed disease, antecedent bone is some 1973), the either in a reasonable large number can manner in crude in children. (Price that cited. or more patients ranging 1971 ; Trifaud and Meary cent that Jeifree precise of fifty for osteosarcoma the five years’ methods (Ohno groups be a factor been indicate of the new adjuvant designed 10 to 25 per tion which carefully from Price are discussed with certain advantages in the light of recent advances with childhood osteosarcoma certainly provides strong survival the Reasons employed are not statistically which method also provided the treatment of choice, perhaps The past situation in connection The bad results of treatment patients of all ages are well known, may of the different methods of treatment had been treated by early amputation, Frankfurt, Hon. Secretary, lnstitut Bristol der Bone Universit#{228}t. Tumour A-l090 Registry, Wien, BRD. BRD. 341 342 C. H. G. PRICE ET TABLE LIST AL I OF CONTRIBUTING CENTRES Number Contributors Price, C. H. G. Zhuber, K., Salzer-Kuntschik, and Salzer, M. Willert, M. Bristol Bone Tumour Registry 49 Vienna Bone Tumour Registry 36 Interdisciplinary Committee German Republic H. G. on Bone Orthopaedic University P. Orthopaedic Republic University Mat#{235}jovsk, Z. Orthopaedic University Clinic, Prague, Keyl, Orthopaedic University Clinic, Munich, lmmenkamp, Groh, M. W. of cases Centre * These cases were collected (Prim. Doz. Dr W. Becker); by: the ZUrich Clinic, Frankfurt, M#{252}nster,West Clinic, Orthopaedic Clinic, (Dr M. Cserhati); Tumours, Homburg. German Saar, West I8 Republic West 12 German 4 Czechoslovakia West University the Surgical 4 German .5 Republic of Frankfurt (Dr Clinic, University N. Sarfert): Heidelberg of Heidelberg (Dr M. Pieper). Age and sex-Table by age and sex. and there was advancing girls, a steady age fifteenth II shows youngest The to years. increase a the of tumour in the maximum There reflecting the distribution child was were usual sixty-six small of the four years cases old, incidence fourteenth boys and with and in over four this series times as common other they as compared at all ages fifty-nine preponderance are 4) tumours at sites common in children; (Price and with I 7 per Jeffree 1973). AGE SEX AND Males DISTRIBUTION Females AND In assessment SURVIVAL Less than 24 Total (years) 24-5 Over 5 1 -6 2 2 1 3 - 1 The - 1 3 -8 3 2 5 -9 4 5 9 1 - -10 5 7 12 2 - -Il 7 9 16 I -12 7 6 13 1 1 -13 9 9 18 2 I -14 II 12 23 -15 14 9 23 Totals 66 59 125 2 - I site distribution of points presented occurred should of tumours-Figure the be in the in the region I shows primary noted: long 1) 96 of the TREATMENT 2 2 4 13 the per of the knee skeletal The following cent of the tumours limbs; 2) 68 per cent ; 3) tumours of the of treatment it is necessary definitive of cure may be been taken as the is, the number at five years from treatment. vast majority of children and It have long bone they die from distant Figure 2 shows the manifestation whose clinical is not sufficient following tumours metastaseschronological of lung metastases and radiographic information points should unusual to find evidence for this be noted: of metastatic thirty months (one out of seventy-seven) tases are unusual (Fig. 2). Although present results at two and a half years, tumours. bones osteosarcoma to be I) 50 per cent of the children (thirty-eight out of seventy-seven) were known to have metastases at five months; and 2) it 2 4 II of records provided determined. The I shows Anatomical for however, to wait so long as this before attemptevaluate and compare the results of treatment. distribution of the first for seventy-five children was 2 of the results (here 96 per cent), usually pulmonary. -7 - OF commencement essential, ing to 1 - cent to define the time when the assumption justified. In the past this has usually five years’ crude survival percentage-that living with or without evident disease the 0-4 -5 arm; II Survival Years of the long bones are unonly 4 per cent in males. EVALUATION TABLE as tumours than the comprise leg that at that time seventy-six spread after and late metasit is not usual to the present study of the seventy-seven patients (98 per cent) had evident metastases. Thus, after two and a half years in most cases a cure may be anticipated, since for long-bone tumours direct invasion of vital organs is a rarity. The disease-free and crude survival curves for longbone tumours (1973) support THE at all ages published this assertion. JOURNAL OF BONE by AND Price JOINT and Jeffree SURGERY OSTEOSARCOMA Fiu. 343 IN CHILDREN I Site of primary FIG. tumour. RESU As might there patients or time T,rnss(ir months) dICer FIG. 57-B, with seven contributory centres were treated by a combination during which by either of both. this series For All the radiotherapy or operation, Owing to the prolonged of cases has been collected disjnosis 2 First appearance of pulmonary metastasis in seventy-seven patients. No information: twenty patients: alive, no metastasis: twenty-eight patients; 50 per cent have metastases at five months; 98 per cent at thirty months. VOL. be expected, LTS was much variety in the methods of treatment. reason these are given in detail in Table III. this z 3 Results of treatment related to site of primary tumour. Black circles: dead with metastasis within two and a half years of the start oftreatment. Stippled circles: alive without metastasis. Upper figure: over two and a halfyears; lower figure: under two and a half years. (**Metastases evident at eight years.) No. 3. AUGUST 1975 (for instance, the 1972) some patients after 1956, mainly differing regimes Bristol group extended received orthovoltage megavoltage therapy of treatment have been from 1946 to irradiation, but was given. The combined into 344 C. H. G. five categories variations Age specified within in Table III, with only group. I I indicates that survivors each and survival-Table appear at any younger age: as compared as compared Tumour site children were half there years is no with girls. and survival alive older minor children, nor (thirteen for for AL cases unsuitable largest group may difference ET boys (Fig. and the free 3)-Seventeen from two and of disease a half at two years the OF TUMOUR, a one children therapy METHOD Site Femur Tibia fifty-seven) was delayed (Groups composed none was These AND 1 . Biopsy and Survival Humerus Alive-no metastasis (years after start of and 13 2 10 7 - 1 2 14 6 - 2 3 6 1 3 5 3 11 55 30 9 45 21 radical with metastases No metastasis 2years I metastasis 2i to 5 years No metastasis over corrected 1 Metastases cent all had and long-bone survival 12 per - tumour of the tibia, and (two) and survived tumour metastases. of somewhat proximal the 5 24-5 5 or more 4 6 Under metastasis 2 40 28 2 - - 20 16 1 - - 25 19 4 4 21 21 -- 3 - 2 1 1 5 3 - figures 1 19 13 4 3 17 2 2 5 125 97 11 4 13 2 14 I 5 97 lOper 3per l2per cent cent cent - and one children with they with for arm -- but had been under ten (Table with a of the with observation years to be those being with nine out children were for less 1* corrected are for other not 77percent 11 lOpercent 4 3 percent 13 12 percent patients statistically 2 - still living. significant (p < 0. 1) ; neverthe- less, immediate appears to give ablation of the best results. the tumour-bearing limb None of the five children with at than tumours sites other the long disease-free at two and a half years (Fig. Local recurrence of primary tumour-After amputation (two). One years with a to five 2 ences respec- of proximal as compared of survival - percentages seventeen and then succumbed that the prognosis may tumours two and a half years. Treatment and survival-The Table Ill avoid the delineation I a tumour tumours --- 1 included middle part of the humerus free from disease for eight incidence 1 - being - 2 1 These - 1 Survival four out of nineteen for the arm compared of eighty-six for the leg. A further eleven alive, - 4 -- of the knee region surviving one child femur, four the distal radius, It is interesting better leg, 6 - 4 cent. tumours of the eighty-five with tumours III, Fig. 3). There were also also Totals 4 1 at 8 years. disease-free 15 per children -- 5 years * of the 2 under No part child bones with biopsy Totals distal Ulna ProximalMiddle Dead and radiotherapy 5. Operation-not tively Other ablation 4. Radiotherapy and and radiotherapy years Distal 20 and ablation Dead Proximal 1 later 3. Biopsy Distal Radius, ablation forthwith 2. Biopsy differ- treatment) middle . radio- SURVIVAL of tumour and of treatment by group Proximal Method twenty- 111 OF TREATMENT and fibula for two ofthe treatment 4) survived. patients (Groups by radio- survived 4), but definitive (Group of surgery treated ablation 3 and whose alone It may be seen that the two and a half years or early ablative out of forty-two or without a halfyears TABLE SITE of with and five for comparison. survivors over with immediate 2). Two patients 125 and and of out treated 1 and therapy with or more, significant PRICE of forty-six operative amputated an event radiotherapy only two patients so treated. investigation limb had Possibly and avoidable. seven Of recurrence out more elaborate pre- examination theatre might twenty-seven recurred was a local immediate in the operating bones 3, Table III). transfemoral of an make tumours locally. This figure to that reported by Lee and Mackenzie (1964) tumour tissue of possible viability in tumours after radiotherapy. such given is similar for residual amputated than DISCUSSION subdivisions adopted of many small groups in of The in results a group reported here of 1 25 children TIlE JOURNAL ofthe treatment indicate OF BONE that AND of osteosarcorna the prognosis JOINT SURGERY may OSTEOSARCOMA be even worse five years’ that of a there between the is of free of avoids and the there are cartilaginous tumours of the recurrences arm. after implies that the essentialfirst be complete control practical purposes, most promising months on under close trial include now With method therapy for occult micrometastases nevertheless, there have been telangiectatic tumour proportion the of primary as (Jaffe, metastatic risk. utterly local time is the effective prevention there can be no doubt principle in any curative ofthe primary tumour. this can only be effected hood regime At present, the in for and ablation. is all the of most may value of this Cortes et al. 1974). is likely to be most is completely and it is employed at the These points earliest again chemochild- figure here reported. In of long-bone tumours are potentially treatment, to significant are rather than with selective trial of this new adjuvant urgent for patients during of which lead chemo- yet be assessed; early reports of prompt amputation, regime of radiotherapy The more Most and Acid rescue in a (Cortes, Holland, Bodey, Sinkovics, Etcubanas, Long, 1974; progress. antimetastatic tory and results. Bishop when for is chemo- after the diagbe continued cannot encouraging the high mortality the high proportion children, effective by amputation. and The adjuvant treatment the primary tumour in favour protracted also 1974). patient’s with view must Traggis removed in delayed therapy the problem metastases, Leavitt this when arguments the more method Although Frei, Obviously, effective tumour the and have expert supervision. at least Adriamycin high-dose Methotrexate with Folinic pulsed multi-drug plan of treatment Wang and Glidewell 1974; Gottlieb, Rodriguez and Burgess 1974; Wilbur, patient there treatment method as possible This should Glatstein amputation or urgent of twelve schemes must be emphasised also that the tumour tissue anywhere in the body continuation ultimate and and destruction The study of adjuvant Hospital its employcontracture for immediate and it of active analytical operations. higher radiotherapy supports of choice, persistence for method is probably unsuitable and is more appropriate for The of this developments Westminster for flexion mutilating or Moreover, the young children difference the latter new therapy, commenced as soon nosis has been established. 1974). ifthe the time several osteosarcoma. of twenty- considerations. but structure. for very out (Steward tumour, the proponents ofthe certain contra-indications fungation, fracture, markedly likewise this been Manchester amputation unsuccessful matches significant other from During corrected alternative treatment or radiotherapy fol- amputation mortality the three years two by selective disease, many five statistically of months Nevertheless, regime admit ment-tumour by in which for is no The of I 2 per cent collected immediate a high persons. rate Registry, results at six such group survived Whereas regimes older survival Tumour children lowed for similar Children’s eight than disease-free 345 IN CHILDREN such curable trials are improvements with manda- in future With cases contributed by seven treatment centres, it becomes quite impossible to express the authors’ thanks individually to the many colleagues who, by referring their cases, have furnished the information on which this analytical study is based. Nevertheless, acknowledgment is here recorded of this prolonged essential collaboration. Technical, clerical and other staff concerned are thanked for their services. Valuable help was given with the Bristol series by Dr E. Michelinakis, Dr G. M. Jeifree and Mrs J. E. Nutt, in collecting the case records and in the extraction of information from the questionnaires. The Bristol Bone Tumour Registry is supported financially by the Cancer Research Campaign. REFERENCES Cortes, E. P., Holland, J. F., Wang, of the American 15, 170. Cortes, E. P., Holland, Association J. J., and Glidewell, for Cancer 0. (1974) Research. Adriamycin Proceedings Tenth and amputation Annual Meeting primary in of the A,nerican osteogenic Society sarcoma. of Clinical Proceedings Oncology, J. F., Wang, J. J., Sinks, L. F., Blom, J., Senn, H., Bank, A., and Glidewell, 0. (1974) Amputation and Adriamycin in primary osteosarcoma. New England Journal of Medicine, 291, 998-1000. Gottlieb, J. A., Bodey, G. 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