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

Bielack, Stefan; Kempf-Bielack, Beate; Delling, G.; Exner, G. U.; Flege, Silke; Helmke, K.; Kotz, R.; Salzer-Kuntschik, M.; Werner, Matthias; Winkelmann, Winfried; Zoubek, A.; Jürgens, Heribert; Winkler, Kurt

doi:10.1200/jco.20.3.776

Cited by 1,465 publications

(1,567 citation statements)

References 57 publications

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“…The theory that good histologic response correlates with improved prognosis has been supported in the literature [9,42]. The use of serial arteriography in our study had a 92.5% rate of accuracy and 100% sensitivity in predicting good tumor response (greater than 90%).…”

Section: Discussionsupporting

confidence: 66%

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

Hugate

Wilkins

Kelly

et al. 2008

Clinical Orthopaedics &Amp; Related Research

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The neoadjuvant treatment of osteosarcoma using intravenous agents has resulted in survival rates of 55% to 77% [3,5,6,20,22,35]. We designed a neoadjuvant chemotherapy protocol using combined intraarterial and intravenous agents to treat high-grade osteosarcoma and malignant fibrous histiocytoma of bone in an attempt to improve survival. We report the results of treating 53 adults (age 18-77 years) diagnosed with nonmetastatic extremity osteosarcoma or malignant fibrous histiocytoma. Preoperative chemotherapy consisted of intravenous doxorubicin followed by intraarterial cisplatinum administered repetitively every 3 weeks for three to five cycles, depending on tumor response assessed by serial arteriography. Dose and duration of cisplatin were adjusted for tumor size. After resection, good responders (90% or greater necrosis) underwent treatment with the same agents and poor responders were treated with alternative agents for longer duration. Minimum followup was 24 months (mean, 111 months; range, 24-235 months). Estimated Kaplan-Meier survival at 10 years was 82% and event-free survival was 79%. Forty-one patients (77%) had a good histologic response and 92% (49 of 53) underwent limbsparing procedures. Local recurrence occurred in two patients (4%). These results compared favorably with those reported in the current literature.

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Section: Discussionsupporting

confidence: 66%

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

Hugate

Wilkins

Kelly

et al. 2008

Clinical Orthopaedics &Amp; Related Research

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“…Adverse survival in childhood acute lymphoblastic leukemia (ALL) is associated with several single nucleotide polymorphisms (SNPs), including MTHFR c.677C>T p.Ala 222 Val, also known to enhance methotrexate toxicity in both ALL and solid tumors. 2,3,6,[13][14][15][16] In osteosarcoma, MTHFR c.677C>T p.Ala 222 Val increased hematological toxicity but did not influence survival. 17 Cisplatin and doxorubicin form helix-distorting DNA adducts resulting in strand breakage and inhibition of replication.…”

Section: Introductionmentioning

confidence: 94%

“…However, approximately 40% patients show a poor response to chemotherapy, with inferior 5-year survival of 45% to 55%. 2 Furthermore, 60% of bone tumor survivors experience severe or disabling chronic health conditions 30 years from diagnosis. 3 Little is known about MAP chemotherapy pharmacogenomics, but information gained from the use of these agents in other malignancies provides insight into potentially critical pathway components.…”

Section: Introductionmentioning

confidence: 99%

Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma

Windsor

Strauss

Kallis

et al. 2011

Cancer

124

144

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BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young people. Efficacy of multiagent MAP (methotrexate, doxorubicin [Adriamycin], cisplatin) chemotherapy may be influenced by multiple cellular pathways. This pilot study aimed to investigate the association of 36 candidate genetic polymorphisms in MAP pathway genes with histological response, survival, and grade 3‐4 chemotherapy toxicity in osteosarcoma. METHODS: Blood samples were obtained from 60 patients who had completed MAP chemotherapy. All patients were manually genotyped for 5 polymorphisms. The remaining 31 polymorphisms were genotyped in 50 patients using the Illumina 610‐Quad microarray. Associations between candidate polymorphisms and histological response, progression‐free survival, and toxicity were estimated using Pearson chi‐square and Fisher exact tests, the Kaplan‐Meier method, the log‐rank test, and the Cox proportional hazards model. RESULTS: Poor histological response was increased in variants of ABCC2 c.24C>T (P = .011) and GSTP1 c.313A>G p.Ile105Val (P = .009), whereas MTHFD1 c.1958G>A p.Arg653Gln was protective (P = .03). Methotrexate toxicity was increased in variants of MTHFR c.1298A>C p.Glu429Ala (P = .038), ABCB1 c.3435T>C Ile145Ile (P = .027), and ABCC2 c.3563T>A p.Val1188Glu (P = .028). Variants of GSTP1 c.313A>G p.Ile105Val were at increased risk of myelosuppression (P = .024) and cardiac damage (P = .008). CONCLUSIONS: This pilot study represents the most comprehensive study to date examining the role of genetic polymorphisms in osteosarcoma. Although small and retrospective, it shows that several polymorphisms appear to significantly influence toxicity and clinical outcome. These deserve prospective validation in the hope of optimizing treatment for resistant disease and reducing the late effects burden. Cancer 2012. © 2011 American Cancer Society.

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“…Talac et al 14 described in their study of spinal sarcomas that residual tumor at the surgical margin, and resection in a piecemeal fashion, resulted in a high recurrence rate that was associated with early mortality. Similarly, a recent review of 1702 patients with high-grade osteosarcoma 5 indicated that failure to achieve a surgical remission of osteosarcoma was associated with increased age, axial site, long history, delayed start of therapy, intralesional surgical resection, and poor response to chemotherapy. However, Gore et al 15 reported a case with long-term survival after intralesional resection of thoracic spine osteosarcoma with multidisciplinary, multimodal approach, using aggressive chemoradiotherapy with surgical resection.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6] Osteosarcoma is a malignant bone tumor that frequently affects patients in their second and third decades of life, however, it is reported there exists two peaks in the incidence of osteosarcoma, one is in the second decade and another in the seventh decade of life. 7 Huvos 8 reported three cases of osteosarcoma of the spine among 117 patients with osteosarcoma older than 60 years.…”

Section: Introductionmentioning

confidence: 99%

Primary osteosarcoma of the thoracic spine: report of an unusual elderly patient with autopsy findings

et al. 2005

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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

Abstract: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

Cited by 1,465 publications

References 57 publications

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma

Primary osteosarcoma of the thoracic spine: report of an unusual elderly patient with autopsy findings

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