Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience.

Hudson, Melissa M.; Jaffe, M. R.; Jaffe, Norman; Ayala, Ana; Raymond, A. Kevin; Carrasco, Humberto; Wallace, Sylvia M.; Murray, John A.; Robertson, Resa

doi:10.1200/jco.1990.8.12.1988

Cited by 177 publications

(112 citation statements)

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“…When IL-2-transduced MNNG cells were included, smaller tumors developed that readily regressed with GCV. A total of 95 of 97 mice (98%) in the experimental groups (1)(2)(3)(4)(5)(6)(7)(8), which contained as little as 5% gene-modified cells, demonstrated full and lasting regression. Two of 97 mice (2%) showed regrowth after an initial disappearance of macroscopic tumor.…”

Section: In Vivo Bystander Effectmentioning

confidence: 99%

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Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes

2000

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Current treatment of osteosarcoma produces disappointing outcomes, and innovative therapies must be investigated. We have used retroviral vectors to transfer the herpes simplex virus thymidine kinase (HSVtk) and interleukin-2 genes to human osteosarcoma cells. Each gene was stably transduced and expressed; the HSVtk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to GCV killing. Human osteosarcoma cells were used to develop a series of experiments in athymic nude mice to treat experimental osteosarcoma. Subcutaneously implanted mixtures of tumor cells and HSVtk vector producer cells developed into tumors that completely regressed upon administration of GCV. Subcutaneously implanted mixtures of transduced and wild-type cells showed a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as 10% of the cells were HSVtk ϩ . A significant (P Ͻ .05) antitumoral response was seen against primary tumors composed of unmodified cells when a secondary tumor of transduced cells was implanted at a distance of 1 cm, suggesting a diffusible bystander factor. The presence of interleukin-2-transduced cells improved the efficacy of treatment. A significant (P Ͻ .03) antitumoral response was seen in the treatment of established osteosarcomas by the injection of HSVtk vector producer cells.

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Section: In Vivo Bystander Effectmentioning

confidence: 99%

“…1,2 It is a primary tumor deriving from primitive bone-forming mesenchyme, characterized by the production of osteoid tissue or immature bone from proliferating spindle cells. 3 The etiology of osteosarcoma is associated with allelic chromosomal deletions, commonly involving the retinoblastoma (RB) and p53 tumor-suppressor genes.…”

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confidence: 99%

Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes

2000

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“…In patients with osteosarcoma, significant prognostic factors for lung metastasis include tumour burden (size) and the proportion of the tumour manifesting necrosis after preoperative chemotherapy. 13 Patients having tumours with a diameter of >15 cm have 3.4 folds higher risk of death, whereas with tumour diameters of <15 cm survival is better. 14 Patients exhibiting small or stable tumour volumes are those whose histology responds favourably to therapy, with a positive predictive value of 88%, 4 but predictive values have not been derived for tumour volumes and lung metastasis.…”

Section: Figurementioning

confidence: 99%

Tumour Volume and Lung Metastasis in Patients with Osteosarcoma

Munajat

Zulmi

Nor-Azman

et al. 2008

J Orthop Surg (Hong Kong)

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Purpose. To assess the association between tumour volume and occurrence of lung metastasis in patients with osteosarcoma and to determine the cut-off value. Methods.Records of 70 patients with histopathologically confirmed primary osteosarcoma in the extremities who had magnetic resonance imaging and computed tomography of the thorax less than one month before treatment were reviewed, with reference to the official report of tumour dimensions and lung metastasis by radiologists. The status of lung metastasis was assessed. Tumour volume was measured using the formula for an ellipsoidal mass. Results. Of the 70 patients with osteosarcoma, 33 (47%) had evidence of lung metastasis. Tumour volume was directly associated with occurrence of lung metastasis (p=0.048). The proportion having lung metastasis when the primary tumour volume exceeded 371 cm 3 was 69%, compared to 34% in those with smaller tumours. Conclusion. Larger tumours are more likely to

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“…Age-related tumor biology and pharmacogenomics of pediatric osteosarcoma need to be explored in order to explain these findings. The percentage of tumor necrosis induced by preoperative chemotherapy had a significant correlation with outcome of pediatric osteosarcoma in previous studies (Hudson et al, 1990). We received an unsatisfactory response since no good responder (tumor necrosis >90%) was observed in our study.…”

Section: Discussionmentioning

confidence: 54%

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

Choeyprasert¹,

Natesirinilkul²,

Charoenkwan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5% respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

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Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience.

Cited by 177 publications

References 0 publications

Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes

Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes

Tumour Volume and Lung Metastasis in Patients with Osteosarcoma

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

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