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Prognostic Significance of Clinical and Post-Neoadjuvant Chemotherapy Associated Histomorphological Parameters in Osteosarcoma: A Retrospective Study from a Tertiary Care CenterFunding Nil
Introduction Osteosarcoma is the most prevalent bone cancer in adolescents. Neoadjuvant chemotherapy (NACT) followed by resection is the current modality of treatment for osteosarcoma. Histological evaluation of extent of tumor necrosis on resection is a well-established prognostic indicator in osteosarcoma correlating with survival in most cases.
Objectives The main objective of this study was to establish prognostic significance of various clinical and histological parameters post-NACT in osteosarcoma and to compare the integrated prognostic index proposed by Chui et al, with grading of response to NACT by Huvos and Rosen for osteosarcoma.
Materials and Methods This is a retrospective study done over a period of four years and includes 47 cases of osteosarcoma treated with NACT. All slides were reviewed and association of various clinical and histological parameters with overall survival was assessed with chi-squared test and Cox-regression analysis.
Results Statistical analysis revealed the prognostic significance of age at presentation, anatomic site, primary tumor size, metastatic status, and clinical stage. Histological parameters such as mitosis ≥10/10hpfs, ≥10% residual tumor were significantly associated with poor survival. Tumor necrosis ≥ 90% (excluding areas of hemorrhage, fibrosis and acellular osteoid) was significantly associated with increased survival. An integrated prognostic index formed by combining above parameters gives a better estimate of overall survival compared with residual disease or necrosis alone.
Conclusion Integrated prognostic index improves prognostication in patients treated for osteosarcoma.
Navatha Vangala and Shantveer G. Uppin were involved in concepts, design, definition of intellectual content, literature search, data acquisition, data analysis, statistical analysis, manuscript preparation, editing, and review. K. Nageshwara Rao, P. Chandrasekhar, and Sadashivudu Gundeti were involved in concepts, definition of intellectual content, literature search, data acquisition, data analysis, manuscript preparation, editing, and review. Navatha Vangala and Shantveer G. Uppin have provided guarantee to this manuscript.
Article published online:
11 December 2021
© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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- 1 Chui MH, Kandel RA, Wong M. et al. Histopathologic features of prognostic significance in high-grade osteosarcoma. Arch Pathol Lab Med 2016; 140 (11) 1231-1242
- 2 Rosen G, Caparros B, Huvos AG. et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 1982; 49 (06) 1221-1230
- 3 Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res 2009; 152: 3-13
- 4 Savage SA, Mirabello L. Using epidemiology and genomics to understand osteosarcoma etiology. Sarcoma 2011; 2011: 548151
- 5 Raymond AK, Chawla SP, Carrasco CH. et al. Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol 1987; 4 (03) 212-236
- 6 Kim SY, Helman LJ. Strategies to explore new approaches in the investigation and treatment of osteosarcoma. Cancer Treat Res 2009; 152: 517-528
- 7 Bacci G, Picci P, Ferrari S. et al. Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer 1993; 72 (11) 3227-3238
- 8 Rosen G, Huvos AG, Mosende C. et al. Chemotherapy and thoracotomy for metastatic osteogenic sarcoma. A model for adjuvant chemotherapy and the rationale for the timing of thoracic surgery. Cancer 1978; 41: 841-849
- 9 Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. 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 (05) 1154-1161
- 10 Harting MT, Lally KP, Andrassy RJ. et al. Age as a prognostic factor for patients with osteosarcoma: an analysis of 438 patients. J Cancer Res Clin Oncol 2010; 136 (04) 561-570
- 11 Pakos EE, Nearchou AD, Grimer RJ. et al. Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 2009; 45 (13) 2367-2375
- 12 Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 1994; 12 (12) 2699-2705
- 13 Bacci G, Balladelli A, Palmerini E. et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities in preadolescent patients: the Rizzoli Institute experience. J Pediatr Hematol Oncol 2008; 30 (12) 908-912
- 14 Bacci G, Mercuri M, Longhi A. et al. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution. Eur J Cancer 2005; 41 (14) 2079-2085
- 15 Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn PC. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 2002; 38 (09) 1218-1225
- 16 McTiernan A, Jinks RC, Sydes MR. et al. Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup. Eur J Cancer 2012; 48 (05) 703-712
- 17 Bentzen SM, Poulsen HS, Kaae S. et al. Prognostic factors in osteosarcomas. A regression analysis. Cancer 1988; 62 (01) 194-202
- 18 Zalupski MM, Rankin C, Ryan JR. et al. Adjuvant therapy of osteosarcoma–a Phase II trial: Southwest Oncology Group study 9139. Cancer 2004; 100 (04) 818-825
- 19 Xing D, Qasem SA, Owusu K, Zhang K, Siegal GP, Wei S. Changing prognostic factors in osteosarcoma: analysis of 381 cases from two institutions. Hum Pathol 2014; 45 (08) 1688-1696
- 20 Lewis IJ, Nooij MA, Whelan J. et al; MRC BO06 and EORTC 80931 collaborators, European Osteosarcoma Intergroup. 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 (02) 112-128
- 21 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 (03) 776-790
- 22 Whelan JS, Jinks RC, McTiernan A. et al. Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials. Ann Oncol 2012; 23 (06) 1607-1616
- 23 Glasser DB, Lane JM, Huvos AG, Marcove RC, Rosen G. Survival, prognosis, and therapeutic response in osteogenic sarcoma. The Memorial Hospital experience. Cancer 1992; 69 (03) 698-708
- 24 Meister P, Konrad E, Lob G, Janka G, Keyl W, Stürz H. Osteosarcoma: histological evaluation and grading. Arch Orthop Trauma Surg 1979; 94 (02) 91-98
- 25 Ohno T, Abe M, Tateishi A, Kako K, Miki H. Osteogenic sarcoma. A study of one hundred and thirty cases. J Bone Joint Surg Am 1975; 57 (03) 397-404
- 26 Min HS, Kang HG, Ro JY. Therapy related changes in osteosarcoma and Ewing sarcoma of bone. Open Pathol J 2009; 3: 99-105
- 27 Lucas DR, Kshirsagar MP, Biermann JS. et al. Histologic alterations from neoadjuvant chemotherapy in high-grade extremity soft tissue sarcoma: clinicopathological correlation. Oncologist 2008; 13 (04) 451-458
- 28 Jetley S, Jairajpuri ZS, Rana S. et al. Tumor histopathological response to neoadjuvant chemotherapy in bone sarcomas: a single-institutional experience. Int J Health Allied Sci 2020; 9: 240-245