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Clinical Orthopaedics and Related Research®

, Volume 472, Issue 8, pp 2506–2513 | Cite as

Paley’s Multiplier Method Does Not Accurately Predict Adult Height in Children with Bone Sarcoma

  • Magdalena Maria Gilg
  • Christine Wibmer
  • Dimosthenis Andreou
  • Alexander Avian
  • Petra Sovinz
  • Werner Maurer-Ertl
  • Per-Ulf Tunn
  • Andreas Leithner
Clinical Research

Abstract

Background

The majority of patients with osteosarcoma and Ewing’s sarcoma are diagnosed before skeletal maturity. Paley’s multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing’s sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy.

Questions/purposes

We asked whether (1) Paley’s formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients.

Methods

Retrospectively, data for 94 patients with osteosarcoma and Ewing’s sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31–124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores).

Results

Height prediction using Paley’s method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, −17 to 8). Patients with osteosarcoma and Ewing’s sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing’s sarcoma.

Conclusions

Owing to its lack of reliability in this patient group, methods other than Paley’s should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy.

Level of Evidence

Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.

Keywords

Osteosarcoma Limb Salvage Adult Height Skeletal Maturity Bone Sarcoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Abed R, Grimer R. Surgical modalities in the treatment of bone sarcoma in children. Cancer Treat Rev. 2010;36:342–347.PubMedCrossRefGoogle Scholar
  2. 2.
    Balamuth NJ, Womer RB. Ewing’s sarcoma. Lancet Oncol. 2010;11:184–192.PubMedCrossRefGoogle Scholar
  3. 3.
    Bath LF, Crofton PM, Evans AE, Ranke MB, Elmlinger MW, Kelnar CJ, Wallace WH. Bone turnover and growth during and after chemotherapy in children with solid tumors. Pediatr Res. 2004;55:224–230.PubMedCrossRefGoogle Scholar
  4. 4.
    Baumgart R, Lenze U. Expandable endoprostheses in malignant bone tumors in children: indications and limitations. Recent Results Cancer Res. 2009;179:59–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Berger D, Engelbrecht R, Mertelsmann R. [The Red Book-Haematology and Internistic Oncology][in German]. Landsberg, Germany: Hüthig Jehle Rehm GmbH; 2006.Google Scholar
  6. 6.
    Bielack S, Flege S, Kempf-Bielack B. [Treatment strategies in osteosarcoma] [in German]. Der Onkologe. 2000;6:747–759.CrossRefGoogle Scholar
  7. 7.
    Carrle D, Bielack SS. Current strategies of chemotherapy in osteosarcoma. Int Orthop. 2006;30:445–451.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Cool WP, Carter SR, Grimer RJ, Tillman RM, Walker PS. Growth after extendible endoprosthetic replacement of the distal femur. J Bone Joint Surg Br. 1997;79:938–942.PubMedCrossRefGoogle Scholar
  9. 9.
    Crofton PM, Ahmed SF, Wade JC, Elmlinger MW, Ranke MB, Kelnar CJ, Wallace WH. Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukemia. Pediatr Res. 2000;48:490–496.PubMedCrossRefGoogle Scholar
  10. 10.
    de Onis M. Update on the implementation of the WHO child growth standards. World Rev Nutr Diet. 2013;106:75–82.PubMedGoogle Scholar
  11. 11.
    de Onis M, Garza C, Victora CG, Onyango AW, Frongillo EA, Martines J. The WHO Multicentre Growth Reference Study: planning, study design, and methodology. Food Nutr Bull. 2004;25(1 suppl):S15–26.PubMedGoogle Scholar
  12. 12.
    Ecklund K, Laor T, Goorin AM, Connolly LP, Jaramillo D. Methotrexate osteopathy in patients with osteosarcoma. Radiology. 1997;202:543–547.PubMedGoogle Scholar
  13. 13.
    Fan C, Foster BK, Wallace WH, Xian CJ. Pathobiology and prevention of cancer chemotherapy-induced bone growth arrest, bone loss, and osteonecrosis. Curr Mol Med. 2011;11:140–151.PubMedCrossRefGoogle Scholar
  14. 14.
    Glasser DB, Duane K, Lane JM, Healey JH, Caparros-Sison B. The effect of chemotherapy on growth in the skeletally immature individual. Clin Orthop Relat Res. 1991;262:93–100.PubMedGoogle Scholar
  15. 15.
    Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford, CA: Stanford University Press; 1959.Google Scholar
  16. 16.
    Groot-Loonen JJ, Otten BJ, van t’Hof MA, Lippens RJ, Stoelinga GB. Chemotherapy plays a major role in the inhibition of catch-up growth during maintenance therapy for childhood acute lymphoblastic leukemia. Pediatrics. 1995;96:693–695.PubMedGoogle Scholar
  17. 17.
    Hokken-Koelega AC, van Doorn JW, Hahlen K, Stijnen T, de Muinck Keizer-Schrama SM, Drop SL. Long-term effects of treatment for acute lymphoblastic leukemia with and without cranial irradiation on growth and puberty: a comparative study. Pediatr Res. 1993;33:577–582.PubMedCrossRefGoogle Scholar
  18. 18.
    Hwang N, Grimer RJ, Carter SR, Tillman RM, Abudu A, Jeys LM. Early results of a non-invasive extendible prosthesis for limb-salvage surgery in children with bone tumours. J Bone Joint Surg Br. 2012;94:265–269.PubMedCrossRefGoogle Scholar
  19. 19.
    Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Juergens H, Craft A. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer. 2006;47:22–29.PubMedCrossRefGoogle Scholar
  20. 20.
    Kotz RI, Windhager R, Dominkus M, Robioneck B, Muller-Daniels H. A self-extending paediatric leg implant. Nature. 2000;406:143–144.PubMedCrossRefGoogle Scholar
  21. 21.
    Ladenstein R, Potschger U, Le Deley MC, Whelan J, Paulussen M, Oberlin O, van den Berg H, Dirksen U, Hjorth L, Michon J, Lewis I, Craft A, Jurgens H. Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol. 2010;28:3284–3291.PubMedCrossRefGoogle Scholar
  22. 22.
    Lewis M. The use of an expandable and adjustable prosthesis in the treatment of childhood malignant bone tumors of the extremity. Cancer. 1986;57:499–502.PubMedCrossRefGoogle Scholar
  23. 23.
    Paley D, Bhave A, Herzenberg JE, Bowen JR. Multiplier method for predicting limb-length discrepancy. J Bone Joint Surg Am. 2000;82:1432–1446.PubMedGoogle Scholar
  24. 24.
    Paley J, Talor J, Levin A, Bhave A, Paley D, Herzenberg JE. The multiplier method for prediction of adult height. J Pediatr Orthop. 2004;24:732–737.PubMedCrossRefGoogle Scholar
  25. 25.
    Parkes SE, Parke S, Mangham DC, Grimer RJ, Davies P, Morland BJ. Fifty years of paediatric malignant bone tumours in the West Midlands, UK, 1957–2006: incidence, treatment and outcome. Paediatr Perinat Epidemiol. 2010;24:470–478.PubMedCrossRefGoogle Scholar
  26. 26.
    Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, Schuck A, Winkelmann W, Kohler G, Poremba C, Zoubek A, Ladenstein R, van den Berg H, Hunold A, Cassoni A, Spooner D, Grimer R, Whelan J, McTiernan A, Jurgens H, European Intergroup Cooperative Ewing’s Sarcoma Study-92. Results of the EICESS-92 study: two randomized trials of Ewing’s sarcoma treatment: cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008;26:4385–4393.PubMedCrossRefGoogle Scholar
  27. 27.
    Pirker-Fruhauf UM, Friesenbichler J, Urban EC, Obermayer-Pietsch B, Leithner A. Osteoporosis in children and young adults: a late effect after chemotherapy for bone sarcoma. Clin Orthop Relat Res. 2012;470:2874–2885.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ritter J, Bielack SS. Osteosarcoma. Ann Oncol. 2010;21(suppl 7):vii320–325.Google Scholar
  29. 29.
    Robson H. Bone growth mechanisms and the effects of cytotoxic drugs. Arch Dis Child. 1999;81:360–364.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Robson H, Anderson E, Eden OB, Isaksson O, Shalet S. Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation. J Endocrinol. 1998;157:225–235.PubMedCrossRefGoogle Scholar
  31. 31.
    Roche AF, Wainer H, Thissen D. The RWT method for the prediction of adult stature. Pediatrics. 1975;56:1027–1033.PubMedGoogle Scholar
  32. 32.
    Sanders JO, Howell J, Qiu X. Comparison of the Paley method using chronological age with use of skeletal maturity for predicting mature limb length in children. J Bone Joint Surg Am. 2011;93:1051–1056.PubMedCrossRefGoogle Scholar
  33. 33.
    Schiller C, Windhager R, Fellinger EJ, Salzer-Kuntschik M, Kaider A, Kotz R. Extendable tumour endoprostheses for the leg in children. J Bone Joint Surg Br. 1995;77:608–614.PubMedGoogle Scholar
  34. 34.
    Schleiermacher G, Peter M, Oberlin O, Philip T, Rubie H, Mechinaud F, Sommelet-Olive D, Landman-Parker J, Bours D, Michon J, Delattre O; Société Française d’Oncologie Pédiatrique. Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized Ewing tumor. J Clin Oncol. 2003;21:85–91.PubMedCrossRefGoogle Scholar
  35. 35.
    Tanner JM, Healy MJR, Goldstein H, Cameron N. Assessment of Skeletal Maturity and Prediction of Adult Height (TW3) Method. 3rd ed. London, UK: WB Saunders; 2001.Google Scholar
  36. 36.
    van Leeuwen BL, Hartel RM, Jansen HW, Kamps WA, Hoekstra HJ. The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton. Eur J Surg Oncol. 2003;29:49–58.PubMedCrossRefGoogle Scholar
  37. 37.
    van Leeuwen BL, Kamps WA, Hartel RM, Veth RP, Sluiter WJ, Hoekstra HJ. Effect of single chemotherapeutic agents on the growing skeleton of the rat. Ann Oncol. 2000;11:1121–1126.PubMedCrossRefGoogle Scholar
  38. 38.
    van Leeuwen BL, Kamps WA, Jansen HW, Hoekstra HJ. The effect of chemotherapy on the growing skeleton. Cancer Treat Rev. 2000;26:363–376.PubMedCrossRefGoogle Scholar
  39. 39.
    Viana MB, Vilela MI. Height deficit during and many years after treatment for acute lymphoblastic leukemia in children: a review. Pediatr Blood Cancer. 2008;50(2 suppl):509–516; discussion 517.PubMedCrossRefGoogle Scholar
  40. 40.
    Winkler K, Bielack S, Delling G, Salzer-Kuntschik M, Kotz R, Greenshaw C, Jurgens H, Ritter J, Kusnierz-Glaz C, Erttmann R, et al. Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). Cancer. 1990;66:1703–1710.PubMedCrossRefGoogle Scholar
  41. 41.
    Xian CJ, Cool JC, Scherer MA, Macsai CE, Fan C, Covino M, Foster BK. Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects. Bone. 2007;41:842–850.PubMedCrossRefGoogle Scholar
  42. 42.
    Xian CJ, Cool JC, van Gangelen J, Foster BK, Howarth GS. Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and metaphyseal bone in rats. Cancer Biol Ther. 2007;6:170–177.PubMedCrossRefGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons® 2014

Authors and Affiliations

  • Magdalena Maria Gilg
    • 1
  • Christine Wibmer
    • 1
  • Dimosthenis Andreou
    • 2
  • Alexander Avian
    • 3
  • Petra Sovinz
    • 4
  • Werner Maurer-Ertl
    • 1
  • Per-Ulf Tunn
    • 5
  • Andreas Leithner
    • 1
  1. 1.Department of Orthopaedic SurgeryMedical University of GrazGrazAustria
  2. 2.Department of General Orthopaedics and TumororthopaedicsUniversity Hospital of MuensterMünsterGermany
  3. 3.Institute for Medical Informatics, Statistics and DocumentationMedical University of GrazGrazAustria
  4. 4.Division of Paediatric Haemato-Oncology, Department of PaediatricsMedical University of GrazGrazAustria
  5. 5.Department of Orthopaedic OncologyHELIOS Klinikum Berlin-BuchBerlinGermany

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