Analysis of Prognostic Factors in Osteosarcoma Adult Patients, a Single Institution Experience
Authors:
D. Adámková Krákorová 1,2; K. Veselý 2,3; I. Zambo 2,3; Š. Tuček 1,2; J. Tomášek 1,2; A. Jurečková 1,2; P. Janíček 2,4; J. Černý 2,4; L. Pazourek 2,4; Š. Ondrůšek 2,4; I. Selingerová 5
Authors‘ workplace:
Klinika komplexní onkologické péče, MOÚ Brno
1; Lékařská fakulta, MU Brno
2; I. patologicko-anatomický ústav, FN u sv. Anny v Brně
3; I. ortopedická klinika, FN u sv. Anny v Brně
4; Ústav matematiky a statistiky, PřF MU Brno
5
Published in:
Klin Onkol 2012; 25(5): 346-358
Category:
Original Articles
Overview
Background:
The objective of this report was to estimate long-term outcome and prognostic factors in adult patients with high-grade osteosarcoma. The intended therapeutic strategy included preoperative and/or postoperative chemotherapy as well as surgery of all operable lesions.
Patients and Metods:
We reviewed the clinical data of 36 newly diagnosed adult patients (aged 19–82, average 37.5, median 28.5 years) with high-grade osteosarcoma of the trunk or limbs evaluted by a multidisciplinary team and treated between 1999 and 2010 in Brno. Forty-five percent of patients were over thirty, more than 36% over forty. Thirty-one percent of patients had metastasis at the time of diagnosis. Demographic parameters, tumor-related and treatment-related variables included possible prognostic factors and their impact on response, overall survival (OS) and event-free survival (EFS) were analyzed.
Results:
All the patients were followed up after treatment. Seventy-three percent of patients were poor responders to chemotherapy. Sixteen patients are alive, and twenty patients died. The survival time ranged from 2 to 177 months (average 45 months, median survival 23 months). The 5-year OS of all patients was 52.4%. OS of patients without metastasis was 68.12%, while 2-year OS with metastasis was 26% only. 5-year EFS was 38.7%. Univariate analysis revealed that the prognosis of adult osteosarcoma patients was significantly related to distant metastasis (p = 0.006), surgical stage (p = 0.00582), serum alkaline phosphatase (ALP) level (p = 0.00841) and serum lactatdehydrogenase (LD) level (p = 0.047). The other analyzed prognostic factors including age had no statistically significant influence on outcome of osteosarcoma in adult patients.
Conclusion:
The prognosis of osteosarcoma in adult patients was significantly correlated to surgical stage, distant metastasis, serum ALP and LD.
Key words:
osteosarcoma – adult – prognostic factors – therapy
Submitted:
20. 6. 2012
Accepted:
7. 8. 2012
Sources
1. Isakoff MF, Harris MJ, Beghart MC et al. Bone Sarcomas. In: Bleyer WA, Barr RD (eds). Cancer in Adolescents and Young Adults. Berlin, Heidelberg, New York: Springer-Verlag 2007: 203–218.
2. Bleyer WA, O’Leary M, Barr R et al. Cancer epidemiology in Older Adolescents and Young Adults 15 to 29 years of Age, including SEER Incidence and Survival, 1975–2000. Bethesda MD: National Cancer Institute 2006.
3. Malawer MM, Helman LJ, Sullivan BO. Sarcomas of Bone. In: De Vita VT, Hellmann S, Rosenberg SA (eds). Cancer Principles and Practise of Oncology. 8th ed. Philadelphia: Lippincot Williams and Wilkins 2008: 1794–1812.
4. Pazdur R, Wagman LD, Camphausen KA et al. Cancer Management: A Multidisciplinary Approach. 12th ed. 2009: 569–583. Available from: http://www.cancernetwork.com/cancer-management-12.
5. NCCN Clinical Practise Guidelines in Oncology. Bone Cancer V 2/2012. Available from: http://www.nccn.org//professionals/physician_gls/PDF/breast.pdf.
6. Carrle D, Bielack SS. Current strategies of chemotherapy in osteosarcoma. Int Orthop 2006: 30(6): 445–451.
7. Bielack SS, Kempf-Bielack B, Delling G et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002; 20(3): 776–790.
8. Longhi A, Errani C, De Paolis M et al. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 2006; 32(6): 423–436.
9. Picci P. Osteosarcoma (osteogenic sarcoma). Orphanet J Rare Diseases 2007; 2: 6.
10. Ferrari S, Palmerini E. Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma. Curr Opin Oncol 2007; 19(4): 341–346.
11. Bacci G, Longhi A, Versaci M et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15 year experience in 789 patients treated at a single institution. Cancer 2006; 106(5): 1154–1161.
12. Ritter J, Bielack SS. Osteosarcoma. Ann Oncol 2010; 21 (Suppl 7): vii320–vii325.
13. Harting ML, Blakely ML. Management of osteosarcoma pulmonary metastases. Semin Pediatr Surg 2006; 15(1): 25–29.
14. Lewis IJ, Nooij MA, Whelan J et al. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst 2007; 99(2): 112–128.
15. DeLaney TF, Park L, Goldberg SI et al. Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys 2005; 61(2): 492–498.
16. Bacci G, Lonhgi A, Bertoni F et al. Primary high-grade osteosarcoma: comparison between preadolescent and older patients. J Pediatr Hematol Oncol 2005; 27(3): 129–134.
17. Goorin AM, Schwartzentruber DJ, Devidas M et al. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 2003; 21(8): 1574–1580.
18. Smeland S, Bruland OS, Hjorth L et al. Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years. Acta Orthop 2011; 82(2): 211–216.
19. Ferrari S, Ruggieri P, Cefalo G et al. Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian Sarcoma Group Trial ISG/OS-1. J Clin Oncol 2012; 30(17): 2112–2118.
20. Hegyi M, Semsei AF, Jakab Z et al. Good prognosis of localized osteosarcoma in young patients treated with limb-salvage surgery and chemotherapy. Pediatr Blood Cancer 2011; 57(3): 415–422.
21. Hagleitner MM, Hoogerbrugge PM, van der Graaf WT et al. Age as prognostic factor in patients with osteosarcoma. Bone 2011; 49(6): 1173–1177.
22. Song WS, Kong CB, Jeon DG et al. Prognosis of extremity osteosarcoma in patients aged 40–60 years: a cohort/case controlled study at a single instituce. Eur J Surg Oncol 2010; 36(5): 483–488.
23. Harting MT, Blakely ML, Jaffe N et al. Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma. J Pediatr Surg 2006; 41(1): 194–199.
24. Kager L, Zoubek A, Pötschger U et al. Primary metastatic ostesarcoma: presentation and outcome of patients treated on neojadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 2003; 21(10): 2011–2018.
25. Sajadi KR, Heck RK, Neel MD et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004; 426: 92–96.
26. Bacci G, Ferrari S, Longhi A et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003; 74(4): 449–454.
27. Bacci G, Forni C, Longhi A et al. Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution. J Surg Oncol 2007; 96(2): 118–123.
28. Grimer RJ, Sommerville S, Warnock D et al. Management and outcome after local recurrence of osteosarcoma. Eur J Cancer 2005; 41(4): 578–583.
29. Crompton BD, Goldsby RE, Weinberg VK et al. Survival after recurrence of osteosarcoma: a 20-year experience at a single institution. Pediatr Blood Cancer 2006; 47(3): 255–259.
30. Nathan SS, Gorlick R, Bukata S et al. Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis. Cancer 2006; 107(7): 1607–1616.
31. Kempf-Bielack K, Bielack SS, Jürgens H et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005; 23(3): 559–568.
32. Ferrari S, Briccoli A, Mercuri M et al. Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol 2003; 21(4): 710–715.
33. Bielack SS, Kempf-Bielack B, Branscheid D et al. Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcome of 249 consecutive cooperative osteosarcoma study group patients. J Clin Oncol 2009; 27(4): 557–565.
34. Bacci A, Briccoli A, Longhi A et al. Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 initially treated with neoadjuvant chemotherapy. Acta Oncol 2005; 44(7): 748–755.
35. Briccoli A, Rocca M, Salone M et al. Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer 2005; 104(8): 1721–1725.
36. Strauss SJ, McTiernan A, Whelan JS. Late relapse of osteosarcoma: implications for follow-up and screening. Pediatr Blood Cancer 2004; 43(6): 692–697.
37. Anninga JK, Gelderblom H, Fiocco M et al. Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur J Cancer 2011; 47(16): 2431–2445.
38. Saylors RL 3rd, Stine KC, Sullivan J et al. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumor: a Pediatric Oncology Group Phase II Study. J Clin Oncol 2001; 19(15): 3463–3469.
39. Merimsky O, Meller I, Flusser G et al. Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study. Cancer Chemother Pharmacol 2000; 45(2): 177–181.
40. Grignani G, Palmerini E, Dileo P et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol 2012; 23(2): 508–516.
41. Loeb DM, Garrrett-Mayer E, Hobbs RF et al. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer 2009; 115(11): 2514–2522.
42. Franzius S, Schuck A, Bielack SS. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002; 20(7): 1953–1954.
43. Anderson P, Kopp L, Anderson N et al. Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing’s sarcoma and osteosarcoma). Expert Opin Investig Drugs 2008; 17(11): 1703–1715.
44. Meyers PA, Schwarz CL, Krailo MD et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol 2008; 26(4): 633–638.
45. Bacci G, Longhi A, Ferrari S et al. Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1,421 patients treated over the last 30 years. Tumori 2004; 90(5): 478–484.
46. Bacci G, Ferrari S, Longhi A et al. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer 2001; 37(1): 32–38.
47. Anninga JK, van de Vijver MJ, Cleton-Jansen AM et al. Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas. Eur J Cancer 2004; 40(7): 963–970.
48. Ferrari S, Bertoni F, Zanella L et al. Evalution of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high--grade osteosarcoma. Cancer 2004; 100(9): 1936–1942.
49. Kruseová J, Mottl H, Kodet R et al. Radikální operační výkon a intenzivní chemoterapie jsou podmínkou úspěšné léčby osteosarkomu. Klin Onkol 2009; 22(4): 168–175.
50. Artells R, Moreno I, Díaz T et al. Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients. Eur J Cancer 2010; 46(3): 642–649.
51. Veselska R, Hermanova M, Loja T et al. Nestin expression in osteosarcomas and derivation of nestin/CD133 positive osteosarcoma cell lines. BMC Cancer 2008; 8: 300.
Další literatura u autora.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2012 Issue 5
Most read in this issue
- Uterine Sarcomas – a Review
- Analysis of Prognostic Factors in Osteosarcoma Adult Patients, a Single Institution Experience
- Bloodstream Infections of the Intravascular Access Devices – Case Reports and Review of the Literature
- BRAF Mutation: a Novel Approach in Targeted Melanoma Therapy