Skip to main content
Erschienen in: Clinical and Translational Oncology 9/2016

07.01.2016 | Research Article

Prognosticating metastatic osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate and delayed metastasectomy: a single center experience of 102 patients

verfasst von: V. Nataraj, S. Rastogi, S. A. Khan, M. C. Sharma, S. Agarwala, S. Vishnubhatla, S. Bakhshi

Erschienen in: Clinical and Translational Oncology | Ausgabe 9/2016

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Data on prognostic factors in patients with metastatic osteosarcoma treated with uniform chemotherapy protocol are lacking. The objective of this study was to analyze demographic data, treatment outcome and prognostic factors for patients with metastatic osteosarcoma at our center treated with a uniform chemotherapy protocol without high dose methotrexate.

Methods

This is a single-institutional data review of patients treated between June 2003 and December 2012 with neoadjuvant chemotherapy, local site surgery followed by adjuvant chemotherapy and metastasectomy at completion of adjuvant chemotherapy.

Results

102 patients of metastatic osteosarcoma were treated with a median age of 18 years (range 8–48 years), male to female ratio of 3.3:1 and median symptom duration of 4 months. EFS and OS at 5 years were 12.7 ± 0.1 and 28.1 ± 0.1 %, respectively. On multivariate analysis, elevated serum alkaline phosphatase (p < 0.001) and number of metastasis >3 (p = 0.04) were predictive of lower EFS, whereas elevated serum alkaline phosphatase (p = 0.01), number of metastasis >3 (p = 0.05), and margin positivity (p < 0.001) were predictive of lower OS.

Conclusions

This is the largest data on metastatic osteosarcoma treated with a uniform chemotherapy protocol without high dose methotrexate. The data showed prognostic factors similar to what have been observed previously such as elevated serum alkaline phosphatase and >3 metastatic lesions in lung predicting inferior outcome. Notably our survival was comparable to data from other studies despite our practice of delaying metastasectomy to completion of chemotherapy rather than performing the same along with local site surgery.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Meyers PA, Heller G, Healey JH, Huvos A, Applewhite A, Sun M, et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol. 1993;11:449–53.PubMed Meyers PA, Heller G, Healey JH, Huvos A, Applewhite A, Sun M, et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol. 1993;11:449–53.PubMed
2.
Zurück zum Zitat Bacci G, Briccoli A, Ferrari S, Saeter G, Donati D, Longhi A, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide. Oncol Rep. 2000;7:339–46.PubMed Bacci G, Briccoli A, Ferrari S, Saeter G, Donati D, Longhi A, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide. Oncol Rep. 2000;7:339–46.PubMed
3.
Zurück zum Zitat Meyer WH, Pratt CB, Poquette CA, Rao BN, Parham DM, Marina NM, et al. Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children’s Research Hospital OS-91 trial. J Clin Oncol. 2001;19:171–82.PubMed Meyer WH, Pratt CB, Poquette CA, Rao BN, Parham DM, Marina NM, et al. Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children’s Research Hospital OS-91 trial. J Clin Oncol. 2001;19:171–82.PubMed
4.
Zurück zum Zitat Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, et al. Treatment of metastatic osteosarcoma at diagnosis: a pediatric oncology group study. J Clin Oncol. 1998;16:3641–8.PubMed Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, et al. Treatment of metastatic osteosarcoma at diagnosis: a pediatric oncology group study. J Clin Oncol. 1998;16:3641–8.PubMed
5.
Zurück zum Zitat Goorin AM, Harris MB, Bernstein M, Ferguson W, Devidas M, Siegal GP, et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. J Clin Oncol. 2002;20:426–33.CrossRefPubMed Goorin AM, Harris MB, Bernstein M, Ferguson W, Devidas M, Siegal GP, et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. J Clin Oncol. 2002;20:426–33.CrossRefPubMed
6.
Zurück zum Zitat Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome–the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome–the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed
7.
Zurück zum Zitat Kaste SC, Liu T, Billups CA, Daw NC, Pratt CB, Meyer WH. Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity. Pediatr Blood Cancer. 2004;43:723–8.CrossRefPubMed Kaste SC, Liu T, Billups CA, Daw NC, Pratt CB, Meyer WH. Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity. Pediatr Blood Cancer. 2004;43:723–8.CrossRefPubMed
8.
Zurück zum Zitat Anninga JK, Gelderblom H, Fiocco M, et al. Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur J Cancer. 2011;47:2431.CrossRefPubMed Anninga JK, Gelderblom H, Fiocco M, et al. Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand? Eur J Cancer. 2011;47:2431.CrossRefPubMed
9.
Zurück zum Zitat Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, Bramwell VH, et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European osteosarcoma intergroup. Lancet. 1997;350:911–7.CrossRefPubMed Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, Bramwell VH, et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European osteosarcoma intergroup. Lancet. 1997;350:911–7.CrossRefPubMed
10.
Zurück zum Zitat Huvos AG, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med. 1977;101:14–8.PubMed Huvos AG, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med. 1977;101:14–8.PubMed
11.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed
12.
Zurück zum Zitat Mostert S, Arora RS, Arreola M, Bagai P, Friedrich P, Gupta S, et al. Abandonment of treatment for childhood cancer: position statement of a SIOP PODC working group. Lancet Oncol. 2011;12:719–20.CrossRefPubMed Mostert S, Arora RS, Arreola M, Bagai P, Friedrich P, Gupta S, et al. Abandonment of treatment for childhood cancer: position statement of a SIOP PODC working group. Lancet Oncol. 2011;12:719–20.CrossRefPubMed
13.
Zurück zum Zitat Kager L, Zoubek A, Pötschger U, Kastner U, Flege S, Kempf-Bielack B, et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2003;21:2011–8.CrossRefPubMed Kager L, Zoubek A, Pötschger U, Kastner U, Flege S, Kempf-Bielack B, et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2003;21:2011–8.CrossRefPubMed
14.
Zurück zum Zitat Meyers PA, Heller G, Healey JH, Huvos A, Applewhite A, Sun M, et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol. 1993;11:449–53.PubMed Meyers PA, Heller G, Healey JH, Huvos A, Applewhite A, Sun M, et al. Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol. 1993;11:449–53.PubMed
15.
Zurück zum Zitat Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome–the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome–the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed
16.
Zurück zum Zitat Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, et al. Treatment of metastatic osteosarcoma at diagnosis: a pediatric oncology group study. J Clin Oncol. 1998;16:3641–8.PubMed Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, et al. Treatment of metastatic osteosarcoma at diagnosis: a pediatric oncology group study. J Clin Oncol. 1998;16:3641–8.PubMed
17.
Zurück zum Zitat Bacci G, Briccoli A, Ferrari S, Longhi A, Mercuri M, Capanna R, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030–9.CrossRefPubMed Bacci G, Briccoli A, Ferrari S, Longhi A, Mercuri M, Capanna R, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030–9.CrossRefPubMed
18.
Zurück zum Zitat Tsuchiya H, Kanazawa Y, Abdel-Wanis ME, Asada N, Abe S, Isu K, et al. Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese musculoskeletal oncology group study. J Clin Oncol. 2002;20:3470–7.CrossRefPubMed Tsuchiya H, Kanazawa Y, Abdel-Wanis ME, Asada N, Abe S, Isu K, et al. Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese musculoskeletal oncology group study. J Clin Oncol. 2002;20:3470–7.CrossRefPubMed
19.
Zurück zum Zitat Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome—the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed Mialou V, Philip T, Kalifa C, Perol D, Gentet J-C, Marec-Berard P, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome—the French pediatric experience. Cancer. 2005;104:1100–9.CrossRefPubMed
20.
Zurück zum Zitat Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, 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;99:112–28.CrossRefPubMed Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, 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;99:112–28.CrossRefPubMed
21.
Zurück zum Zitat Marina N, Smeland S, Bielack SS et al (2014) MAPIE vs MAP as postoperative chemotherapy in patients with a poor response to preoperative chemotherapy for newly-diagnosed osteosarcoma: results from EURAMOS-1 (Paper 032). Presented at: Connective Tissue Oncology Society (CTOS). Marina N, Smeland S, Bielack SS et al (2014) MAPIE vs MAP as postoperative chemotherapy in patients with a poor response to preoperative chemotherapy for newly-diagnosed osteosarcoma: results from EURAMOS-1 (Paper 032). Presented at: Connective Tissue Oncology Society (CTOS).
22.
Zurück zum Zitat Bacci G, Mercuri M, Briccoli A, Ferrari S, Bertoni F, Donati D, et al. Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions. Cancer. 1997;79:245–54.CrossRefPubMed Bacci G, Mercuri M, Briccoli A, Ferrari S, Bertoni F, Donati D, et al. Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions. Cancer. 1997;79:245–54.CrossRefPubMed
23.
Zurück zum Zitat Goorin AM, Delorey MJ, Lack EE, Gelber RD, Price K, Cassady JR, et al. Prognostic significance of complete surgical resection of pulmonary metastases in patients with osteogenic sarcoma: analysis of 32 patients. J Clin Oncol. 1984;2:425–31.PubMed Goorin AM, Delorey MJ, Lack EE, Gelber RD, Price K, Cassady JR, et al. Prognostic significance of complete surgical resection of pulmonary metastases in patients with osteogenic sarcoma: analysis of 32 patients. J Clin Oncol. 1984;2:425–31.PubMed
24.
25.
Zurück zum Zitat Wu PK, Chen WM, Chen CF, Lee OK, Haung CK, Chen TH. Primary osteogenic sarcoma with pulmonary metastasis: clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol. 2009;39:514–22.CrossRefPubMed Wu PK, Chen WM, Chen CF, Lee OK, Haung CK, Chen TH. Primary osteogenic sarcoma with pulmonary metastasis: clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol. 2009;39:514–22.CrossRefPubMed
26.
Zurück zum Zitat Bacci G, Ferrari S, Sangiorgi L, Picci P, Casadei R, Orlandi M, et al. Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities. J Chemother Florence Italy. 1994;6:204–10.CrossRef Bacci G, Ferrari S, Sangiorgi L, Picci P, Casadei R, Orlandi M, et al. Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities. J Chemother Florence Italy. 1994;6:204–10.CrossRef
27.
Zurück zum Zitat Marina NM, Pratt CB, Rao BN, Shema SJ, Meyer WH. Improved prognosis of children with osteosarcoma metastatic to the lung (s) at the time of diagnosis. Cancer. 1992;70:2722–7.CrossRefPubMed Marina NM, Pratt CB, Rao BN, Shema SJ, Meyer WH. Improved prognosis of children with osteosarcoma metastatic to the lung (s) at the time of diagnosis. Cancer. 1992;70:2722–7.CrossRefPubMed
28.
Zurück zum Zitat Bacci G, Picci P, Briccoli A, Avella M, Ferrari S, Femino FP, et al. Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions). Tumori. 1992;78:200–6.PubMed Bacci G, Picci P, Briccoli A, Avella M, Ferrari S, Femino FP, et al. Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions). Tumori. 1992;78:200–6.PubMed
Metadaten
Titel
Prognosticating metastatic osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate and delayed metastasectomy: a single center experience of 102 patients
verfasst von
V. Nataraj
S. Rastogi
S. A. Khan
M. C. Sharma
S. Agarwala
S. Vishnubhatla
S. Bakhshi
Publikationsdatum
07.01.2016
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 9/2016
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1467-8

Weitere Artikel der Ausgabe 9/2016

Clinical and Translational Oncology 9/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.