Osteosarcoma: improvement in survival limited to high-grade patients only

Jawad, Muhammad Umar; Cheung, Michael C.; Clarke, Jennifer; Koniaris, Leonidas G.; Scully, Sean P.

doi:10.1007/s00432-010-0923-7

Cited by 91 publications

(80 citation statements)

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“…With advances in the medical management of musculoskeletal malignancies, patient survival has improved substantially [11]. Thus, specific means to address aseptic failure, the primary cause of EPR failure at intermediate to long term, are needed.…”

Section: Introductionmentioning

confidence: 99%

Aseptic Failure: How Does the Compress® Implant Compare to Cemented Stems?

Pedtke

Wustrack

Fang

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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Background Failure of endoprosthetic reconstruction with conventional stems due to aseptic loosening remains a challenge for maintenance of limb integrity and function. The Compress 1 implant (Biomet Inc, Warsaw, IN, USA) attempts to avoid aseptic failure by means of a unique technologic innovation. Though the existing literature suggests survivorship of Compress 1 and stemmed implants is similar in the short term, studies are limited by population size and followup duration.Questions/purposes We therefore compared (1) the rate of aseptic failure between Compress 1 and cemented intramedullary stems and (2) evaluated the overall intermediate-term implant survivorship. Methods We reviewed 26 patients with Compress 1 implants and 26 matched patients with cemented intramedullary stems. The patients were operated on over a 3-year period. Analysis focused on factors related to implant survival, including age, sex, diagnosis, infection, aseptic loosening, local recurrence, and fracture. Minimum followup was 0.32 years (average, 6.2 years; range, 0.32-9.2 years).

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Section: Introductionmentioning

confidence: 99%

Aseptic Failure: How Does the Compress® Implant Compare to Cemented Stems?

Pedtke

Wustrack

Fang

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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“…However, the OR estimates for an age of sixty years or more (OR = 2.04; 95% CI, 1.53 to 2.73), an axial tumor location (OR = 2.10; 95% CI, 1.56 to 2.84), and a low composite SES score (OR = 1.62; 95% CI, 1.08 to 2.42) were similar to those in the analysis that eliminated cases with missing tumor size information. It has been demonstrated previously, and it is well accepted, that patients with metastatic disease at initial presentation have a poorer prognosis than those with localized disease [3][4][5][6][7][8][9][10] . Bacci et al reported an overall survival rate of 94% at two years for osteosarcoma patients with localized disease compared with 55% for those with metastatic disease at presentation 4 .…”

mentioning

confidence: 97%

“…Many previous studies have revealed an association of increasing age with a poorer prognosis in patients with osteosarcoma [5][6][7]10,16,17 . However, there is substantial uncertainty and debate regarding whether age itself is a risk factor or is simply a surrogate for other, more important, aspects of the disease.…”

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confidence: 99%

“…An estimated 15% to 20% of individuals with osteosarcoma have identifiable metastases at initial presentation [1][2][3] , and these patients have a far worse prognosis compared with patients with localized disease only 1,[3][4][5][6][7][8][9][10] . There is a paucity of data regarding clinical characteristics associated with a greater risk of distant metastatic disease at diagnosis 5 .…”

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confidence: 99%

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Risk Factors for Metastatic Disease at Presentation with Osteosarcoma

Miller

Cram

Lynch

et al. 2013

Journal of Bone and Joint Surgery

156

126

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“…effective chemotherapy, the five-year survival rate for patients treated with intensive multidrug chemotherapy and aggressive local control has been reported at 55-80% (3,20,21). However, chemotherapy may fail to eliminate all osteosarcoma cells due to intrinsic or acquired drug resistance, which is the most frequent cause of tumor recurrence and results in a poor clinical outcome (22).…”

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confidence: 99%

LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy

Long

Zhong

Peng

et al. 2014

Molecular Medicine Reports

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Abstract.Pirarubicin is frequently used in chemotherapy against tumors. However, clinical use is severely limited by the development of progressive dose-dependent cardiomyopathy and acquired drug resistance. LY294002 is a commonly used pharmacologic inhibitor, which selectively inhibits the phosphoinositide 3-kinase-AKT nexus. The aim of this study was to investigate the combined inhibitory effect of LY294002 and pirarubicin on human osteosarcoma (OS) cells in vitro. The inhibitory effect of LY294002 plus pirarubicin on U2-OS and MG-63 OS cell proliferation, apoptosis, migration and invasion was investigated by cell proliferation, wound healing and Transwell invasion assays. The results revealed that LY294002 and pirarubicin synergistically induced apoptosis, and inhibited the growth, migration and invasion of OS cells. This indicates that LY294002 enhanced the effects of pirarubicin on OS in vitro. LY294002 combined with pirarubicin may thus be a future therapeutic strategy in OS. IntroductionOsteosarcoma (OS) is the most common type of malignant tumor of the bone. Due to the rapid and aggressive nature of the disease, the standard treatment for OS was previously amputation of the affected limb; however, the cure rate associated with this method was <10% and almost all patients succumbed to their disease within one year from initial diagnosis. Over the past three decades, with the development of effective chemotherapeutic agents, the five-year cumulative survival rate of primary OS patients has significantly improved to 60-90% (1-7). Chemotherapy is, thus, an important treatment for OS.Pirarubicin, a member of the anthracycline family, is widely applied in the treatment of OS (8-12). However, its clinical use is severely limited by the development of progressive dose-dependent cardiomyopathy and acquired drug resistance (13). Adjunctive drug therapies occasionally reduce adverse reactions and drug resistance. Therefore, drugs that enhance the effect of pirarubicin against OS are being investigated.The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is important in tumor cell differentiation, cell cycle, apoptosis, growth and metastasis (8,9). Recent studies have shown that the PI3K/AKT signaling pathway is crucially involved in the resistance of cancer cells to chemotherapy (14,15). Therefore, inhibition of the PI3K/AKT signaling pathway is under investigation as a potential target for cancer therapy. LY294002 is a commonly used pharmacological PI3K inhibitor, which acts on the ATP-binding site of the PI3K enzyme and thus selectively inhibits the PI3K-AKT nexus. Numerous studies have demonstrated that LY294002 enhances the chemosensitivity of various cancer types to a wide variety of drugs (16)(17)(18)(19). However, whether LY294002 enhances the effects of pirarubicin on OS remains unclear.In the present study, the effect of LY294002 on the sensitivity of OS cell lines to pirarubicin chemotherapy was investigated, in addition to the possible mechanisms underlying any such effect. Materials and methodsCel...

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Osteosarcoma: improvement in survival limited to high-grade patients only

Abstract: The level of evidence for this article is 2.

Cited by 91 publications

References 50 publications

Aseptic Failure: How Does the Compress® Implant Compare to Cemented Stems?

Aseptic Failure: How Does the Compress® Implant Compare to Cemented Stems?

Risk Factors for Metastatic Disease at Presentation with Osteosarcoma

LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy

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