Osteosarcoma in Pre-adolescent Patients

Cho, W H; Lee, S Y; Song, Won Seok; Park, J H

doi:10.1177/147323000603400614

Cited by 13 publications

(10 citation statements)

References 22 publications

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“…This would suggest that preoperative chemotherapy is less effective in younger children. Likewise, Cho [33] reported good responses in only 2 (20%) of 10 children under 7 years of age. These results, together with the high frequency of metastases at diagnosis promote the hypothesis of a different tumour biology in young children, with more aggressive disease.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

et al. 2011

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BackgroundOsteosarcoma is the most common primary bone malignancy in childhood and adolescence. However, it is very rare in children under 5 years of age. Although studies in young children are limited in number, they all underline the high rate of amputation in this population, with conflicting results being recently reported regarding their prognosis.MethodsTo enhance knowledge on the clinical characteristics and prognosis of osteosarcoma in young children, we reviewed the medical records and histology of all children diagnosed with osteosarcoma before the age of five years and treated in SFCE (Société Française des Cancers et leucémies de l'Enfant) centers between 1980 and 2007.ResultsFifteen patients from 7 centers were studied. Long bones were involved in 14 cases. Metastases were present at diagnosis in 40% of cases. The histologic type was osteoblastic in 74% of cases. Two patients had a relevant history. One child developed a second malignancy 13 years after osteosarcoma diagnosis.Thirteen children received preoperative chemotherapy including high-dose methotrexate, but only 36% had a good histologic response. Chemotherapy was well tolerated, apart from a case of severe late convulsive encephalopathy in a one-year-old infant. Limb salvage surgery was performed in six cases, with frequent mechanical and infectious complications and variable functional outcomes.Complete remission was obtained in 12 children, six of whom relapsed. With a median follow-up of 5 years, six patients were alive in remission, seven died of their disease (45%), in a broad range of 2 months to 8 years after diagnosis, two were lost to follow-up.ConclusionsOsteosarcoma seems to be more aggressive in children under five years of age, and surgical management remains a challange.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

et al. 2011

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“…Bacci reported 68% of patients treated by limb‐salvage surgery and Ferrari found this procedure in 83% of the patients. In other two studies, limb salvage procedure was possible in up to 90% of patients .…”

Section: Discussionmentioning

confidence: 91%

“…An important consideration is the exclusion of metastatic patients in some studies such as the manner in which age has been converted to a categorical variable. Some authors have evaluated children as the person who has not yet completed 12 years of age , while others have defined children as all under 10 years of age and still others have used a cut‐off set at 14‐year old .…”

Section: Discussionmentioning

confidence: 99%

“…An important consideration is the exclusion of metastatic patients in some studies [10][11][12] such as the manner in which age has been converted to a categorical variable. Some authors have evaluated children as the person who has not yet completed 12 years of age [8,9,11], while others have defined children as all under 10 years of age [6,9,22] and still others have used a cut-off set at 14-year old [12,14]. The present institutional review of OST in children and AYA did not reveal any significant prognostic factor among the following variables: metastases at diagnosis, tumor size, and grade of necrosis, except between symptom onset and diagnosis that might be due the high level of parental monitoring for younger children.…”

Section: Discussionmentioning

confidence: 99%

“…Age at diagnosis as a significant prognostic factor for patients with OST is however controversial. While some authors have described a lack of association between age and prognosis [4][5][6][7][8][9][10], others have reported a worse prognosis for children [11,12], and still others have reported children fared better than adolescents and adults [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Osteosarcoma in patients younger than 12 years old without metastases have similar prognosis as adolescent and young adults

Eleutério

Senerchia

Almeida

et al. 2015

Pediatric Blood & Cancer

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Background Childhood cancer is relatively rare and tends to present specific age distribution, as a prognostic factor for some of these diseases. Information on how young age affects prognosis, response to chemotherapy, and local control options in children versus AYA with osteosarcoma (OST) is minimal. Methods In order to identify the main differences in clinicalpathologic features, surgical approaches and survival rates of primary high grade OST of the extremity between children (n = 156; <12 years old) and AYA (n = 397; 12–30 years old), the institutional database with 553 patients treated by BOTG studies over 15 years were reviewed. Results There were no differences in metastasess at diagnosis, tumor size, and grade of necrosis between the two age groups. The rate of amputation was 30% higher in the children group (P = 0.018). The rate of limb salvage surgery using reconstruction with allograft or autograft was 70% higher in the children group (P = 0.018) while endoprosthesis rate was 40% higher in the AYA group (P = 0.018). The log rank test revealed that survival is similar between the two age groups for non‐metastatic patients (P = 0.424 for OS and P = 0.393 for EFS). Metastatic patients of both ages group had higher risk of dying compared to non‐metastatic (HR 3.283 95% CI 2.581–4.177; P < 0.001). Children with metastases at diagnosis had less OS time (P = 0.049) and EFS time (P = 0.032) than adolescents. Conclusion Non‐metastatic OST in preadolescent patients does not appear to be significantly differentfrom those seen in AYA patients, but has local control challenges. Children presenting with metastases should be considered an ultra‐high‐risk group. Pediatr Blood Cancer 2015;62:1209–1213. © 2015 Wiley Periodicals, Inc.

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Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK‐3β/β‐catenin signaling

Liang

Liu

et al. 2017

J of Cellular Biochemistry

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Osteosarcoma (OS) is the most malignant primary bone tumor in children and adolescents with limited treatment options and poor prognosis. Recently, aberrant expression of Runx2 has been found in OS, thereby contributing to the development, and progression of OS. However, the upstream signaling molecules that regulate its expression in OS remain largely unknown. In the present study, we first confirmed that the inhibition of HSP90 with 17-AAG caused significant apoptosis of OS cells via a caspase-3-dependent mechanism, and that inhibition or knockdown of HSP90 by 17-AAG or siRNAs significantly suppressed mRNA and protein expression of Runx2. Furthermore, we provided evidence that Runx2 was transcriptionally regulated by HSP90 when using MG132 and CHX chase assay. We also demonstrated that β-catenin was overexpressed in OS tissue, and that knockdown of β-catenin induced pronounced apoptosis of OS cells in the presence or absence of 17-AAG.Interestingly, this phenomenon was accompanied with a significant reduction of Runx2 and Cyclin D1 expression, indicating an essential role of Runx2/Cyclin D1 in 17-AAG-induced cells apoptosis. Moreover, we demonstrated that the apoptosis of OS cells induced by 17-AAG did require the involvement of the AKT/GSK-3β/ β-catenin signaling pathway by using pharmacological inhibitor GSK-3β (LiCl) or siGSK-3β. Our findings reveal a novel mechanism that Runx2 is transcriptionally

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Osteosarcoma in Pre-adolescent Patients

Cited by 13 publications

References 22 publications

Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases

Osteosarcoma in patients younger than 12 years old without metastases have similar prognosis as adolescent and young adults

Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK‐3β/β‐catenin signaling

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