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Longitudinal Growth Following Treatment for Osteosarcoma

Longitudinal Growth Following Treatment for Osteosarcoma Purpose. The pur pos e o f this s tudy w as t o a na lyse t he h eight a t d i agnosi s a nd g rowth i n 7 2 skeletal ly i mm a ture c hildren who h ad b een t reated f or os teos arcoma i n t he a rea o f the k ne e. Subjects. Of the p atients , t he a verage a ge a t d i agno sis w as 1 0 years i n g irls a nd 1 2 years i n b oys. A l l c hildr en r eceived ne o- adjuv ant c hemo therapy , a nd h ad l imb s alvage b y e ndo prosth etic r eplaceme nt. Re sults and c onclusion. The resul ts o f this s tudy i ndi cate t hat t here is n o e vide nc e that c hildren w ith o steosa rcom a a re taller a t d iagnos is t han t heir n or ma l c oun terpart s. H owe ver, there was a m a rked r etardat ion i n g row th i n t he y ear fo llowing the a dmi nistrati on o f cytot oxic c hemo therapy . T here were 19 childr en w ho r eached s ke letal m a tur ity. T he ® nal h eight i n these c hildren w as n o t s igni® c antly d i fferent fr om t he n or ma l p op ulation . Key words: he ight, longitudinal growth, o steosarcoma , c hemotherapy . Int roduc tion and Pyle me thod . Height w as also me a sured i n t he patien t s, while s tandi ng w ith a level p el vis. It h as bee n r epor ted t hat c h ildr en w ith o s teo sarcoma Fo llowi ng d i agn os is, all patient s rec ei ved n eo - are taller t ha n thei r nor mal cou nt erparts. However, adjuvant c h em o t herapy accor di ng t o t he t he n c u r - 2,3 thi s has bee n c o nt radi ct ed b y other s. rent p rotoco l. Th is was nor mally ci splatinu m a nd Glasser et al. showed t hat c hi ldr en w ith m a ligna nt do xo r ub icin o r cisplatinu m , do xo rub ici n a nd h igh - primary bone t um o ur s had a ma rked r etarda tion i n do se m e t hot rexa te. gr owth d u ring t he y ea r of cy tot oxi c c hem o ther apy. After three c ycl es o f ch em o ther apy (usua lly 9 Th ey also sugge s ted t hat t he ir ® na l heigh t m i ght b e wee ks following d iagno s is), patient s wer e r estage d affected. and u n de r wen t l imb -salvage s urge ry. Li mb salvage It w as the p urpose o f this study to a nalyse t he was performe d b y resec tion o f the t um o ur and e nd o - heigh t a t d i agno s is and t he g r owth t ha t h ad oc cur red prosthet ic r ep laceme n t. T h e e xp ec ted g r owth i n t he in s kelet ally imm a tur e c hildr en w ith a n os teo sarcoma resect ed s egm e nt w as ca lcul ated w ith t he a id of the around t he k ne e w ho h ave bee n t reated b y limb bone a ge a nd d a ta provided b y Tu p man. If the salvage a t o u r c e nt re. ex pe ct ed g r owth i n t he r esect ed s egm e nt e xc ee de d 3 c m , an ex ten s ible end o prosthetic r eplacem e n t w as 8± 10 inserted, other wise a no n- ext en s ible r eplace me n t Su b j ect s and me t hod s that a llowed s ome n o rmal gr owth t o c on t inue w as 10± 12 All s keletally i mm a tur e c h ildr en w ho were d i agn os ed used. betwe e n 1 9 81 a nd 1 9 9 4 a s having a n os teo sarcoma Pa tient s wer e d i scharge d a fter 2 w ee ks and h ad a in t he a rea of the k nee , t hat h ad been t reated a t o ur further t hree c y cles o f ch emo t herapy. All c hildr en ce nt re b y limb -salvage s urger y, wer e i nc lud e d i n t his wer e f ollowed -up in t he o u t pa tient c l ini c a nd h ad study . Pa tien t s were e x cl ud e d i f they d i ed w ithin 1 . 5 thei r height e stima ted a t r egu l ar int er vals un t il t hey yea rs of di agn o sis, or if hei gh t m e a surem e nt s wer e reach ed s keletal m a tur ity. Children w ho had an un a vailable. ex ten sible prosthesis had regu l ar len g then i ng s i n At d i agn o sis, all patient s wer e f ully staged a nd h ad or de r to m a intain l imb len gt h e qua lity. On a verage , the ir b one a ge e stima ted a ccor ding t o t he G reu lich two l eng t heni ng o peration s per yea r, from time o f Co rrespon dence t o: W. P. Co ol, W alnut C o ttage, U pton M a gna, S hropshire S Y4 4TZ, UK. Tel: 1 44 1691 404000 page 1 47 (daytime ) 1 44 1743 709210; E-Ma il: p cool@n etcomu k.co.uk . 1357-714X/ 9 8/020115± 05 Ó 1998 Ca rfax P ublishing L t d 116 W. Paul Cool et al. di agn o sis un t il t hey rea ch ed s keleta l ma turity , wer e performed. Th e h eigh ts at d i agn os is of all childr en w ere p lot- 14,15 ted i n t he g row th c h arts for Br itish ch ildren acc or di ng t o g ui de l ine s gi ven b y Col e. Th e c h ildr en w er e s plit i nt o t hr ee g r oup s. On e gr oup of patien t s bel ow t he 2 5 th p er ce nt ile, one gr oup betwe e n t he 2 5 t h a nd 7 5 t h p er ce nt iles and on e g r oup above t he 7 5 t h p ercen t ile. S tatistic al analysis was per formed w ith t he a id of the C hi- square test. Th e h ei gh ts of the c h ildr en 1 a nd 5 y ears follow- ing d iagno s is, and a t s keletal m a tur ity, were a lso plotted i n t he g r owth c harts. Statistic a l analysis was performed i n a ma nne r ide nt ica l to t ha t d e scribe d above. Th e s tandard de v iation s cor e ( or Z sco re) i s the act ual h ei gh t o f the p atient m i nu s the m e a n hei gh t of the p opulation f or that c h ronologi cal a ge d i vided by the a ppropriate s tanda rd de v iation. Th er ef ore, a standa rd de viation s co re o f 0 i nd i ca tes that t he patient h as an average h eight f or age a nd g en d er . Simi larly, a child w ith a sco re o f 1 1, is one s tan- da rd de viation a bove a verage f or age a nd g en d er . Th e d ifferen c e i n s tanda rd de v iation s co re a t d i ag- no s is and 1 y ea r follow ing t rea tme n t i s a me asure f or the v el oc ity o f gr owth. A differen c e i n s tandard de v iation s co re o f 0 i nd i ca tes that t he c h ild had an average v el oc ity o f gr owth f or that a ge r ange . Th e s tanda rd de v iation s cor e w as ca lcu lated f or all patient s who had thei r heigh t e stima ted a t d i ag- no s is and a fter 1 y ear following t rea tme n t . T h e di fferen c e i n s tanda rd de v iation s co re a fter 1 y ear Fig. 1. Difference in bo ne age and c hronological ag e at di agnosis in 72 c hildr en with an osteosarcoma i n the ar ea o f t he knee. A was calcul ated ( ne ga tive i s a de cr ea se in s tandard negative val ue indicates that the bo ne ag e was l ess than the de v iation s cor e) . S imi larly, the d i fference i n s tan- chronological age. da rd de viation s co re w as ca lcul ated 5 y ears follow- ing t reatme nt a nd a t s keletal m a tur ity. All p atient s had thei r bone a ge e stima ted a t t ime of di agn os is. Th e b one a ge w as es timated a cc ordi ng and d o x or ubicin i n c om b ination w ith h igh -dos e 4 6 to t he m e thod d es cr ibed b y Greul ich and P y le and me t ho trexa te. Of the r ema ining 1 2 c h ildren , ni ne co mp ared t o c hr ono log i cal a ge . had che mo t he rapy accor ding t o t he r eg ime p ro- posed b y Rosen et al. and t hree c h ildren h ad alter na tive t reatme nt p rotoc ol s. Results Th ere w er e 2 2 c hildr en w ho event ua lly di ed . Seven t y-two c hi ldr en w ere i den t i® e d f rom the m e di - Tw ent y d e a ths were d u e t o m e t astatic d i sease, one ca l reco rds. Th ere w ere 4 7 b oys and 2 5 g i rls. Th e du e t o d ox o rubicin-ind uc e d c a rdiom y opathy, and average a ge a t d iagno s is was 12 . 1 y ea rs (rang e 5 . 8± on e p atient d i ed d u e t o e xt ens ive ileo femo r al throm- 15 . 3) i n b oys and 9 . 9 y ea rs (range 5 . 8± 13 .5) i n g i rls. bosis. All b ut o ne p atient d i ed w ithi n 5 y ears of In 3 5 c ases the l eft l eg w as affected a nd i n 3 7 c ases di agn o sis, but n o p atient d ied p rior to 1 . 5 y ea rs the r igh t l eg . T h ere w ere 4 5 c h ildren w ho had a follow ing d i agno s is. di stal femor al, and 2 7 w ho h ad a proxima l tibial, Th e b one a ge a t d i agno s is was on a verage 9 . 7 os teo sarcoma . Li mb salvage w as by an en do p ros- yea rs (rang e 6 ± 13 ) i n g i rls and 1 1 . 3 y ears (rang e the tic r eplace me n t t hat c o ul d b e l en gt hen ed i n 5 0 5± 14 ) i n b oys. As ca n be s ee n i n F i g. 1, the v ast ch ildren . Th e r ema ining 2 2 c h ildren h ad an end o - ma jority of ch ildren h ad a bone a ge t hat w as les s prosthet ic r eplacem e nt t ha t c o ul d n o t b e l en g th- than the c hr onol og ical a ge ( on a verage 0 . 25 y ea rs in en e d, but t hat a llowed f or some g rowt h t o gi rls and 0 . 73 y ea rs in b oys). Th is di fference w as 10± 12 continue. statisti cally signi ® c a nt ( sign t es t, p, 0.05). All c h ildr en r ecei ved n e o -adjuvant c hem o ther apy. Th ere w ere 6 3 p atien ts w ho h ad their h eight Fo rty-three c h ildr en r ec ei ved c i splatinum and d o x - es timated a t d iagno s is. Th e r esults are shown i n F i g. or ub icin o nl y, and 1 7 c hildr en r ec ei ved c isplatinu m 2. Th er e w as no s tatisti cally sign i ® c ant d i fferen ce Longitudinal growth f ollowing treat ment for osteosar coma 117 Fig. 2. He ight at di agnosis in 63 c hildren with an osteosarcoma Fig. 3. He ight 1 y ear f ollowing di agnosis in 50 c hildr en who in the area o f t he knee pl otted in the growth char ts for t he norma l received n eo-adj uvant chemo therapy for a n osteosarcoma i n the 14,15 population. ar ea o f t he kn ee plotted in the growth char ts for t he norma l 14,15 population. betwe e n t he c hi ldr en i n o u r s tud y and t he p opu- than the s tanda rd dev iation s cor e a t d i agn o sis. Bo ys 14,15 lation n o rm. had a standa rd de viation s co re t hat w as on a verage In 5 0 c h ildr en, the h ei gh t w as me a sured 1 y ear 0. 25 l ess than that a t d i agn os is. follow ing d i agn o sis (Fi g 3 ). T h e h ei gh ts in t hes e Th ere w er e 1 9 c h ildr en i n o u r study who rea ch ed ch ildren w ere a lso no t s ign i ® c ant ly d i fferen t f rom skeleta l ma tur ity. Th e ® na l heigh t i n t hese c hildr en 14,15 the n o rmal population. Fo r ty-one o f thes e 50 was not s ign i ® c ant ly d ifferent f rom the n or mal ch ildren a lso had their h eight e stima ted a t d i agn o sis. population ( Fi g 5 ) . S ixt een o f these c hi ldr en a lso As can b e s een i n F i g. 4, the v ast ma jority of had the ir h ei gh t e s timated a t d i agn o sis. Th e s tan- ch ildren h ad a standa rd de v iation s co re t hat w as les s da rd de viation s co re i n g irls w ho reach ed s keletal tha n the s tanda rd de v iation s cor e a t d i agn os is. In ma tur ity was, on a verage, 0. 48 h igh er than that a t gi rls, the s tanda rd dev iation s co re 1 y ear follow ing di agn o sis, whilst this was 0. 24 h igh er in b oys. di agn o sis was, on a verage , 0 . 67 l es s than that a t Th ese r esults ind i ca te t hat t he s urviving c hildr en di agn o sis, whilst thi s was 0. 30 l es s in b oys. Th is subseq uent ly m a ke up for the r etarda tion i n g r owth di fferen c e w as statisti cally sign i ® c ant ( sign t est, ca used b y the c h em o ther apeut ic t reatme nt . A l- p, 0. 05 ) , indi ca ting t hat c hem o ther apy ca uses re- thou g h t he n u m b er of ch ildren w ho reach ed s keletal tardati on i n g r owth i n t he y ear follow ing t rea tme n t . ma tur ity is relativ ely small, ® na l height d o es no t 14,15 At 5 y ears follow ing d i agn o sis, 18 c hildr en h ad seem to b e d i fferen t fr om the p opulation n o rm. the ir h ei gh t m e a sured . Th e h ei gh ts in t hese c hi ldr en were a lso no t s ign i® c a ntly d i fferen t f rom the n o rmal Discussion 14,15 popul ation . Fi ftee n o f thes e ch ildr en a lso had the ir h eight m e a sured a t d i agn o sis. In g irls, the Th is study failed to r eprodu ce t he e arlier ® ndi ng s of standa rd dev iation s cor e w as, on a verage , 0. 17 l es s Fraumeni, sugg e sting t hat c hi ldr en w ith o steo sar- 118 W. Paul Cool et al. Fig. 5. He ight at ske letal ma t urity in 19 c hildr en who hav e be en treated for a n osteosarcoma i n the ar ea o f t he kn ee plotted 14,15 in the growth charts f or t he norma l p opulation. Fig. 4. Difference in standard d eviat ion score after 1 y ear in 41 childr en who ha d th eir height estimat ed at di ag nosis and a f ter 1 year. A n egative va lue indicates that the child h a d a l ess than av erag e growth for a g e and g ender . admi ni stration o f cy tot oxi c c he mo t he rapy. Th is fur- ther illus trates that a ct ua l hei gh t i s a poor ind i ca tor of gr owth r et arda tion a nd t hat t he v el oc ity o f gr owth is a mo r e s en sitive m e asure. co ma are taller t ha n the n or mal population. Ot h- Th e ® na l hei gh t o f the c h ildr en i n t his stud y was 2,3 ers also cou l d n o t ® nd s uch a relation . 14,15 similar to t he n o rmal population . Fu r thermo re, Os teog e ni c s arcoma is mo re c om m o n i n t he s e- the d i fference i n s tanda rd de v iation s cor e w as, on co nd d ec ade o f life, dur ing i nc r ea sed skelet al average, p ositive. Th is ind i cates that t hes e childr en gr owth. It s eems ther ef ore likel y tha t t he i nc iden c e subseq uent ly m a ke up for the r etarda tion i n g r owth of os teos arcoma is related t o t he v eloc ity o f gr owth ca used b y the c h em o t her apy treatme nt . at t ime o f di agno s is rather tha n the h ei gh t a t d i ag- In c on c lus ion, ther e i s no e v idenc e t hat c hildr en no s is. Unfo rtun a tely, no p re- diagno s tic h ei gh t m e a - with o s teos arcoma are taller tha n their n or mal cou n- surem e nt s were a vailable f rom the c hi ldr en i n t his terparts. Growth i s ret arde d i n t he y ea r following study . Th is ma kes it d i f® cul t t o d r aw any co nc lu- ch emo t herapy treatme n t, b ut t he ® na l hei gh t i n sions. Howe ver, i t i s int eresti ng t o n o te t hat t he v ast thes e chi ldr en i s no t s ign i® c a ntly differen t f rom the ma jority of ch ildr en h ad a bone a ge a t d i agn os is that no rmal popul ation . was les s than thei r ch ronologi ca l age . It m i gh t b e tha t t he se c hildr en w ere c atch ing u p on t hei r relative References skeleta l imm a tur ity and h ad an inc r ea sed v el oc ity o f gr owth a t t ime o f di agn os is. 1 Fr aume ni J F. St atur e and m a lignant t um o rs o f bone in c hildhoo d a nd a dol escence . Cancer 1967; 20:967± Th e h ei gh t 1 y ea r following c h em o t herapy trea t- me n t w as also no t s igni ® c a ntly d i fferent f rom the 2 Gl asser D B, Dua ne K, L ane J M, et al. The effect of 14,15 popul ation n o rm. Howe v er, ther e w as a chemo t herapy o n g row th i n t he s keletal ly i mm a tur e sign i ® c ant r ed uc t ion i n s tanda rd de v iation s core, ind ividu al. Clin Orthop 1991; 262:93± 100. indi ca ting t ha t g r owth i s retarde d fo llow ing t he 3 Operska lski E A, Preston- Ma rtin S , H ende rson B E , et Longitudinal growth f ollowing treat ment for osteosar coma 119 al. A c ase-con trol s tudy o f os teos arcoma i n y oun g thetic r eplacem e nt s fo r ma lignant t um o ur s. I n: persons. Am J Epidemi ol 1987; 126:118± 26. Lang lais F , Tom e no B , eds. Li mb s al vag eÐ ma jor r e- 4 Gr eulich W W, Pyle SI . Ra d i ograph ic atlas of s ke letal constructions in oncologic and n ontumoral c onditions . de velopment of t he han d a n d wrist . 2nd e d. S tanford : Be rlin: S p ringer-V erlag, 1 991: 573± 8. Stanfor d U n i versity P ress, 1966. 11 Cool W P, Gr ime r RJ, C arter SR, et al. The sliding 5 Bu rwell R G , Ve rno n C L, Dang er® eld P H. Skeletal component. J Bone Joint Surg (Br) 1995; 77B (Suppl me asureme nt. I n: O wen R , Go odfe llow J , Bu llou gh P , 3):330. eds. Scienti® c foundations of o rthopaedic s an d trauma tol- 12 Inglis A E , Walker P S, Sneath R S , et al. Uncemented ogy. Lon don : W illiam H einema nn, 1980: 317± 29. int rame dul lary ® xation o f imp lants u sing polyethy lene 6 Br amw ell V HC , Bu rgers M , Sne ath R , et al. A com- sleeves, a r oentgen ograph ic s tudy . Clin Orthop 1992; parison o f two s hort i ntens ive a djuv ant c hemo therapy 284:208± 14. regime ns i n o perabl e o steosa rcoma o f limb s i n c hil- 13 Cool W P, Gr ime r RJ , Carter SR, et al. The outcome dr en a nd y oung adu lts: T he ® rst s tudy o f the e ur opean of extensi ble e nd opros thetic r eplaceme nts o f the d istal os teos arcoma i nt ergrou p. J Clin Oncol 1992; 10:1579± femur a nd p roxima l t ibia. J Bone Joint Surg (Br) 1996; 91. 78B (Sup pl 1 ):58. 7 Tupma n G S . A s tudy o f bon e g row th i n n orma l 14 Child G r owth F o und ation. Bo ys g rowth c hart, U n i ted children a nd i ts r elations hip t o s keletal m a turatio n . J Ki ng do m c ros s s ectiona l r eference data 1 994/1. Bone Joint Surg (Br) 1962; 44B:42± 67. 15 Child G r owth F oun da tion. Gi rls g rowth c hart, U n i ted 8 Scales J T, Sn eath R S. The extend ing prosthes is. I n: Ki ng do m c ros s s ectiona l r eference data 1 994/1. Coomb s R , Fr iedland l er G e ds. Bone tumour ma n age- 16 Cole T J. Do g rowth c entile c harts n eed a f ace lift? Br ment. Lond on: Bu tterwor ths, 1 987: 168± 77. M ed J 1994; 308:641± 2. 9 Scales J T, Sneath R S , W right K W J. Design a nd c lini - 17 Ro sen G , Caparros B , H uv os A G , et al. Preoperative cal u se o f extendi ng p rosthe ses. I n: E nne king W F, e d. chemo t herapy f or os teog enic s arcom a : s election o f Li mb s alva ge in mu sculoskeletal oncology . New York: postope rative a djuvan t c hemo therapy b ased o n t he Chur chill L ivingsto ne , 1987: 52± 61. respon se o f the p rima ry t umo r to p reop erative c hemo - 10 Sne ath R S , C arter SR, G r ime r RJ . Gr ow ing e ndo pros- therapy. Cancer 1982; 49:1221± 30. 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Longitudinal Growth Following Treatment for Osteosarcoma

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Hindawi Publishing Corporation
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Copyright © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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1357-714X
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1369-1643
DOI
10.1080/13577149878073
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Abstract

Purpose. The pur pos e o f this s tudy w as t o a na lyse t he h eight a t d i agnosi s a nd g rowth i n 7 2 skeletal ly i mm a ture c hildren who h ad b een t reated f or os teos arcoma i n t he a rea o f the k ne e. Subjects. Of the p atients , t he a verage a ge a t d i agno sis w as 1 0 years i n g irls a nd 1 2 years i n b oys. A l l c hildr en r eceived ne o- adjuv ant c hemo therapy , a nd h ad l imb s alvage b y e ndo prosth etic r eplaceme nt. Re sults and c onclusion. The resul ts o f this s tudy i ndi cate t hat t here is n o e vide nc e that c hildren w ith o steosa rcom a a re taller a t d iagnos is t han t heir n or ma l c oun terpart s. H owe ver, there was a m a rked r etardat ion i n g row th i n t he y ear fo llowing the a dmi nistrati on o f cytot oxic c hemo therapy . T here were 19 childr en w ho r eached s ke letal m a tur ity. T he ® nal h eight i n these c hildren w as n o t s igni® c antly d i fferent fr om t he n or ma l p op ulation . Key words: he ight, longitudinal growth, o steosarcoma , c hemotherapy . Int roduc tion and Pyle me thod . Height w as also me a sured i n t he patien t s, while s tandi ng w ith a level p el vis. It h as bee n r epor ted t hat c h ildr en w ith o s teo sarcoma Fo llowi ng d i agn os is, all patient s rec ei ved n eo - are taller t ha n thei r nor mal cou nt erparts. However, adjuvant c h em o t herapy accor di ng t o t he t he n c u r - 2,3 thi s has bee n c o nt radi ct ed b y other s. rent p rotoco l. Th is was nor mally ci splatinu m a nd Glasser et al. showed t hat c hi ldr en w ith m a ligna nt do xo r ub icin o r cisplatinu m , do xo rub ici n a nd h igh - primary bone t um o ur s had a ma rked r etarda tion i n do se m e t hot rexa te. gr owth d u ring t he y ea r of cy tot oxi c c hem o ther apy. After three c ycl es o f ch em o ther apy (usua lly 9 Th ey also sugge s ted t hat t he ir ® na l heigh t m i ght b e wee ks following d iagno s is), patient s wer e r estage d affected. and u n de r wen t l imb -salvage s urge ry. Li mb salvage It w as the p urpose o f this study to a nalyse t he was performe d b y resec tion o f the t um o ur and e nd o - heigh t a t d i agno s is and t he g r owth t ha t h ad oc cur red prosthet ic r ep laceme n t. T h e e xp ec ted g r owth i n t he in s kelet ally imm a tur e c hildr en w ith a n os teo sarcoma resect ed s egm e nt w as ca lcul ated w ith t he a id of the around t he k ne e w ho h ave bee n t reated b y limb bone a ge a nd d a ta provided b y Tu p man. If the salvage a t o u r c e nt re. ex pe ct ed g r owth i n t he r esect ed s egm e nt e xc ee de d 3 c m , an ex ten s ible end o prosthetic r eplacem e n t w as 8± 10 inserted, other wise a no n- ext en s ible r eplace me n t Su b j ect s and me t hod s that a llowed s ome n o rmal gr owth t o c on t inue w as 10± 12 All s keletally i mm a tur e c h ildr en w ho were d i agn os ed used. betwe e n 1 9 81 a nd 1 9 9 4 a s having a n os teo sarcoma Pa tient s wer e d i scharge d a fter 2 w ee ks and h ad a in t he a rea of the k nee , t hat h ad been t reated a t o ur further t hree c y cles o f ch emo t herapy. All c hildr en ce nt re b y limb -salvage s urger y, wer e i nc lud e d i n t his wer e f ollowed -up in t he o u t pa tient c l ini c a nd h ad study . Pa tien t s were e x cl ud e d i f they d i ed w ithin 1 . 5 thei r height e stima ted a t r egu l ar int er vals un t il t hey yea rs of di agn o sis, or if hei gh t m e a surem e nt s wer e reach ed s keletal m a tur ity. Children w ho had an un a vailable. ex ten sible prosthesis had regu l ar len g then i ng s i n At d i agn o sis, all patient s wer e f ully staged a nd h ad or de r to m a intain l imb len gt h e qua lity. On a verage , the ir b one a ge e stima ted a ccor ding t o t he G reu lich two l eng t heni ng o peration s per yea r, from time o f Co rrespon dence t o: W. P. Co ol, W alnut C o ttage, U pton M a gna, S hropshire S Y4 4TZ, UK. Tel: 1 44 1691 404000 page 1 47 (daytime ) 1 44 1743 709210; E-Ma il: p cool@n etcomu k.co.uk . 1357-714X/ 9 8/020115± 05 Ó 1998 Ca rfax P ublishing L t d 116 W. Paul Cool et al. di agn o sis un t il t hey rea ch ed s keleta l ma turity , wer e performed. Th e h eigh ts at d i agn os is of all childr en w ere p lot- 14,15 ted i n t he g row th c h arts for Br itish ch ildren acc or di ng t o g ui de l ine s gi ven b y Col e. Th e c h ildr en w er e s plit i nt o t hr ee g r oup s. On e gr oup of patien t s bel ow t he 2 5 th p er ce nt ile, one gr oup betwe e n t he 2 5 t h a nd 7 5 t h p er ce nt iles and on e g r oup above t he 7 5 t h p ercen t ile. S tatistic al analysis was per formed w ith t he a id of the C hi- square test. Th e h ei gh ts of the c h ildr en 1 a nd 5 y ears follow- ing d iagno s is, and a t s keletal m a tur ity, were a lso plotted i n t he g r owth c harts. Statistic a l analysis was performed i n a ma nne r ide nt ica l to t ha t d e scribe d above. Th e s tandard de v iation s cor e ( or Z sco re) i s the act ual h ei gh t o f the p atient m i nu s the m e a n hei gh t of the p opulation f or that c h ronologi cal a ge d i vided by the a ppropriate s tanda rd de v iation. Th er ef ore, a standa rd de viation s co re o f 0 i nd i ca tes that t he patient h as an average h eight f or age a nd g en d er . Simi larly, a child w ith a sco re o f 1 1, is one s tan- da rd de viation a bove a verage f or age a nd g en d er . Th e d ifferen c e i n s tanda rd de v iation s co re a t d i ag- no s is and 1 y ea r follow ing t rea tme n t i s a me asure f or the v el oc ity o f gr owth. A differen c e i n s tandard de v iation s co re o f 0 i nd i ca tes that t he c h ild had an average v el oc ity o f gr owth f or that a ge r ange . Th e s tanda rd de v iation s cor e w as ca lcu lated f or all patient s who had thei r heigh t e stima ted a t d i ag- no s is and a fter 1 y ear following t rea tme n t . T h e di fferen c e i n s tanda rd de v iation s co re a fter 1 y ear Fig. 1. Difference in bo ne age and c hronological ag e at di agnosis in 72 c hildr en with an osteosarcoma i n the ar ea o f t he knee. A was calcul ated ( ne ga tive i s a de cr ea se in s tandard negative val ue indicates that the bo ne ag e was l ess than the de v iation s cor e) . S imi larly, the d i fference i n s tan- chronological age. da rd de viation s co re w as ca lcul ated 5 y ears follow- ing t reatme nt a nd a t s keletal m a tur ity. All p atient s had thei r bone a ge e stima ted a t t ime of di agn os is. Th e b one a ge w as es timated a cc ordi ng and d o x or ubicin i n c om b ination w ith h igh -dos e 4 6 to t he m e thod d es cr ibed b y Greul ich and P y le and me t ho trexa te. Of the r ema ining 1 2 c h ildren , ni ne co mp ared t o c hr ono log i cal a ge . had che mo t he rapy accor ding t o t he r eg ime p ro- posed b y Rosen et al. and t hree c h ildren h ad alter na tive t reatme nt p rotoc ol s. Results Th ere w er e 2 2 c hildr en w ho event ua lly di ed . Seven t y-two c hi ldr en w ere i den t i® e d f rom the m e di - Tw ent y d e a ths were d u e t o m e t astatic d i sease, one ca l reco rds. Th ere w ere 4 7 b oys and 2 5 g i rls. Th e du e t o d ox o rubicin-ind uc e d c a rdiom y opathy, and average a ge a t d iagno s is was 12 . 1 y ea rs (rang e 5 . 8± on e p atient d i ed d u e t o e xt ens ive ileo femo r al throm- 15 . 3) i n b oys and 9 . 9 y ea rs (range 5 . 8± 13 .5) i n g i rls. bosis. All b ut o ne p atient d i ed w ithi n 5 y ears of In 3 5 c ases the l eft l eg w as affected a nd i n 3 7 c ases di agn o sis, but n o p atient d ied p rior to 1 . 5 y ea rs the r igh t l eg . T h ere w ere 4 5 c h ildren w ho had a follow ing d i agno s is. di stal femor al, and 2 7 w ho h ad a proxima l tibial, Th e b one a ge a t d i agno s is was on a verage 9 . 7 os teo sarcoma . Li mb salvage w as by an en do p ros- yea rs (rang e 6 ± 13 ) i n g i rls and 1 1 . 3 y ears (rang e the tic r eplace me n t t hat c o ul d b e l en gt hen ed i n 5 0 5± 14 ) i n b oys. As ca n be s ee n i n F i g. 1, the v ast ch ildren . Th e r ema ining 2 2 c h ildren h ad an end o - ma jority of ch ildren h ad a bone a ge t hat w as les s prosthet ic r eplacem e nt t ha t c o ul d n o t b e l en g th- than the c hr onol og ical a ge ( on a verage 0 . 25 y ea rs in en e d, but t hat a llowed f or some g rowt h t o gi rls and 0 . 73 y ea rs in b oys). Th is di fference w as 10± 12 continue. statisti cally signi ® c a nt ( sign t es t, p, 0.05). All c h ildr en r ecei ved n e o -adjuvant c hem o ther apy. Th ere w ere 6 3 p atien ts w ho h ad their h eight Fo rty-three c h ildr en r ec ei ved c i splatinum and d o x - es timated a t d iagno s is. Th e r esults are shown i n F i g. or ub icin o nl y, and 1 7 c hildr en r ec ei ved c isplatinu m 2. Th er e w as no s tatisti cally sign i ® c ant d i fferen ce Longitudinal growth f ollowing treat ment for osteosar coma 117 Fig. 2. He ight at di agnosis in 63 c hildren with an osteosarcoma Fig. 3. He ight 1 y ear f ollowing di agnosis in 50 c hildr en who in the area o f t he knee pl otted in the growth char ts for t he norma l received n eo-adj uvant chemo therapy for a n osteosarcoma i n the 14,15 population. ar ea o f t he kn ee plotted in the growth char ts for t he norma l 14,15 population. betwe e n t he c hi ldr en i n o u r s tud y and t he p opu- than the s tanda rd dev iation s cor e a t d i agn o sis. Bo ys 14,15 lation n o rm. had a standa rd de viation s co re t hat w as on a verage In 5 0 c h ildr en, the h ei gh t w as me a sured 1 y ear 0. 25 l ess than that a t d i agn os is. follow ing d i agn o sis (Fi g 3 ). T h e h ei gh ts in t hes e Th ere w er e 1 9 c h ildr en i n o u r study who rea ch ed ch ildren w ere a lso no t s ign i ® c ant ly d i fferen t f rom skeleta l ma tur ity. Th e ® na l heigh t i n t hese c hildr en 14,15 the n o rmal population. Fo r ty-one o f thes e 50 was not s ign i ® c ant ly d ifferent f rom the n or mal ch ildren a lso had their h eight e stima ted a t d i agn o sis. population ( Fi g 5 ) . S ixt een o f these c hi ldr en a lso As can b e s een i n F i g. 4, the v ast ma jority of had the ir h ei gh t e s timated a t d i agn o sis. Th e s tan- ch ildren h ad a standa rd de v iation s co re t hat w as les s da rd de viation s co re i n g irls w ho reach ed s keletal tha n the s tanda rd de v iation s cor e a t d i agn os is. In ma tur ity was, on a verage, 0. 48 h igh er than that a t gi rls, the s tanda rd dev iation s co re 1 y ear follow ing di agn o sis, whilst this was 0. 24 h igh er in b oys. di agn o sis was, on a verage , 0 . 67 l es s than that a t Th ese r esults ind i ca te t hat t he s urviving c hildr en di agn o sis, whilst thi s was 0. 30 l es s in b oys. Th is subseq uent ly m a ke up for the r etarda tion i n g r owth di fferen c e w as statisti cally sign i ® c ant ( sign t est, ca used b y the c h em o ther apeut ic t reatme nt . A l- p, 0. 05 ) , indi ca ting t hat c hem o ther apy ca uses re- thou g h t he n u m b er of ch ildren w ho reach ed s keletal tardati on i n g r owth i n t he y ear follow ing t rea tme n t . ma tur ity is relativ ely small, ® na l height d o es no t 14,15 At 5 y ears follow ing d i agn o sis, 18 c hildr en h ad seem to b e d i fferen t fr om the p opulation n o rm. the ir h ei gh t m e a sured . Th e h ei gh ts in t hese c hi ldr en were a lso no t s ign i® c a ntly d i fferen t f rom the n o rmal Discussion 14,15 popul ation . Fi ftee n o f thes e ch ildr en a lso had the ir h eight m e a sured a t d i agn o sis. In g irls, the Th is study failed to r eprodu ce t he e arlier ® ndi ng s of standa rd dev iation s cor e w as, on a verage , 0. 17 l es s Fraumeni, sugg e sting t hat c hi ldr en w ith o steo sar- 118 W. Paul Cool et al. Fig. 5. He ight at ske letal ma t urity in 19 c hildr en who hav e be en treated for a n osteosarcoma i n the ar ea o f t he kn ee plotted 14,15 in the growth charts f or t he norma l p opulation. Fig. 4. Difference in standard d eviat ion score after 1 y ear in 41 childr en who ha d th eir height estimat ed at di ag nosis and a f ter 1 year. A n egative va lue indicates that the child h a d a l ess than av erag e growth for a g e and g ender . admi ni stration o f cy tot oxi c c he mo t he rapy. Th is fur- ther illus trates that a ct ua l hei gh t i s a poor ind i ca tor of gr owth r et arda tion a nd t hat t he v el oc ity o f gr owth is a mo r e s en sitive m e asure. co ma are taller t ha n the n or mal population. Ot h- Th e ® na l hei gh t o f the c h ildr en i n t his stud y was 2,3 ers also cou l d n o t ® nd s uch a relation . 14,15 similar to t he n o rmal population . Fu r thermo re, Os teog e ni c s arcoma is mo re c om m o n i n t he s e- the d i fference i n s tanda rd de v iation s cor e w as, on co nd d ec ade o f life, dur ing i nc r ea sed skelet al average, p ositive. Th is ind i cates that t hes e childr en gr owth. It s eems ther ef ore likel y tha t t he i nc iden c e subseq uent ly m a ke up for the r etarda tion i n g r owth of os teos arcoma is related t o t he v eloc ity o f gr owth ca used b y the c h em o t her apy treatme nt . at t ime o f di agno s is rather tha n the h ei gh t a t d i ag- In c on c lus ion, ther e i s no e v idenc e t hat c hildr en no s is. Unfo rtun a tely, no p re- diagno s tic h ei gh t m e a - with o s teos arcoma are taller tha n their n or mal cou n- surem e nt s were a vailable f rom the c hi ldr en i n t his terparts. Growth i s ret arde d i n t he y ea r following study . Th is ma kes it d i f® cul t t o d r aw any co nc lu- ch emo t herapy treatme n t, b ut t he ® na l hei gh t i n sions. Howe ver, i t i s int eresti ng t o n o te t hat t he v ast thes e chi ldr en i s no t s ign i® c a ntly differen t f rom the ma jority of ch ildr en h ad a bone a ge a t d i agn os is that no rmal popul ation . was les s than thei r ch ronologi ca l age . It m i gh t b e tha t t he se c hildr en w ere c atch ing u p on t hei r relative References skeleta l imm a tur ity and h ad an inc r ea sed v el oc ity o f gr owth a t t ime o f di agn os is. 1 Fr aume ni J F. St atur e and m a lignant t um o rs o f bone in c hildhoo d a nd a dol escence . Cancer 1967; 20:967± Th e h ei gh t 1 y ea r following c h em o t herapy trea t- me n t w as also no t s igni ® c a ntly d i fferent f rom the 2 Gl asser D B, Dua ne K, L ane J M, et al. The effect of 14,15 popul ation n o rm. 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