Survival after recurrent osteosarcoma: Data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials

Gelderblom, Hans; Jinks, Rachel C; Sydes, Matthew R.; Bramwell, Vivien; Glabbeke, M. van; Grimer, R. J.; Hogendoorn, Pancras C.W.; McTiernan, Anne; Lewis, Ian; Nooij, M.; Taminiau, A. H. M.; Whelan, Jeremy

doi:10.1016/j.ejca.2010.11.036

Cited by 118 publications

(121 citation statements)

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“…(2) As with most sarcomas, osteosarcomas initially metastasise haematogenously, most commonly to the lungs. …”

Section: Discussionmentioning

confidence: 99%

Rare occurrence of bilateral breast and peritoneal metastases from osteogenic sarcoma

Chan¹,

Kumar²,

Vijayananthan³

2013

smedj

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A 16-year-old Chinese girl was diagnosed with right tibial osteosarcoma 18 months prior to her current presentation. She had undergone resection of the tumour, followed by insertion of an endoprosthesis and chemotherapy. Histopathological examination found 80% tumour necrosis with minimal local tumour invasion.Thoracic CT at the time of diagnosis was normal. A bone scan performed four months after the completion of treatment demonstrated increased radiotracer uptake at the inferior angle of the left scapula, corresponding to a lytic lesion visualised on radiographs, which was consistent with metastasis. However, follow-up thoracic CT remained normal, and she subsequently defaulted treatment.Nine months later, the patient presented to a private gynaecologist with a one-week history of abdominal pain.Ultrasonography examination revealed the presence of a large central mesenteric mass. The uterus and ovaries were normal.A preliminary diagnosis of metastatic tumour was made and she was referred to our hospital for further assessment. Despite being slightly pale, the patient's vital signs were stable, and there was no tachypnoea. Multiple skin nodules less than 5 cm in size located in the inframammary region of the anterior chest wall were seen. ABSTRACT Breast metastases are uncommon and typically spread from contralateral breast carcinomas. Breast metastases that spread from extramammary malignancies are even less common, and account for 0.5%-6.6% of all malignant breast disease. As extrapulmonary metastases from osteosarcoma are uncommon, breast metastasis from osteosarcoma is extremely rare. We report a case of breast and peritoneal metastases from a tibial osteosarcoma 18 months after diagnosis, and 9 months after surgery and adjuvant chemotherapy. Computed tomography findings of multiple calcified and noncalcified tumour deposits in the lungs, pleura, peritoneum, chest wall and both breasts are described.Keywords: breast metastases, cutaneous metastases, osteosarcoma, peritoneal metastases F i g . 1 P o s t e r o a n t e r i o r c h e s t r a d i o g r a p h s h o w s m u l t i p l e l u n g metastases, some of which are calcified (arrowheads), and lobulated right perihilar lymph nodes (arrow).

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“…(2) As with most sarcomas, osteosarcomas initially metastasise haematogenously, most commonly to the lungs. …”

Section: Discussionmentioning

confidence: 99%

Rare occurrence of bilateral breast and peritoneal metastases from osteogenic sarcoma

Chan¹,

Kumar²,

Vijayananthan³

2013

smedj

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“…Combinatory therapeutic approaches, such as surgery together with systemic chemotherapy, are therefore required for the effective treatment of this cancer (1,4). Previous research (5) has shown that osteoclasts can be used as a potential therapeutic target in osteosarcoma, due to their prominence within the tumor and their critical function in bone resorption at sites of microfracture or bone destruction.…”

Section: Introductionmentioning

confidence: 99%

Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma cells

Xie

et al. 2014

Molecular Medicine Reports

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Abstract. The purpose of the present study was to investigate the effects of bafilomycin A1 (BafA1) on proliferation, apoptosis and autophagy in MG63 osteosarcoma cells. The growth rate of MG63 cells was determined using a Cell Counting Kit-8 assay. The mitochondrial membrane potential (Δψ) was measured using a fluorescent probe, JC-1, and the inhibition of autophagy and apoptosis was monitored by transmission electron microscopy. In addition, the inhibition of autophagy was monitored by western blot analysis of microtubule-associated protein 1 light chain 3 (LC3), and the ratio of LC3-II/LC3-I protein levels was calculated as an indicator of the extent of autophagy. Furthermore, the expression levels of specific proteins associated with autophagy, including p53, Beclin1 and p62, were detected in cultured MG63 cells by western blotting. It was shown that the viability of MG63 cells was inhibited following the use of BafA1, and an induction in the expression levels of the apoptosis-related protein p53 and the autophagic protein Beclin1 was detected. Furthermore, a collapse in Δψ was observed, together with an induction of apoptotic cell death, following treatment with BafA1. Therefore, following BafA1-mediated inhibition of autophagy, the inhibition of MG63 cell proliferation and induction of apoptosis were observed.

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“…In case of relapse, the survival probability significantly decreases in relation to time and pattern of recurrence and possibility of achieving a second surgical remission, whereas the role of rescue chemotherapy treatment is not well defined yet [109][110][111]. In addition to the fact that the role of chemotherapy to rescue recurrent HGOS patients is still under discussion, there is no evidence about the best second-line drugs that should be used in this situation.…”

Section: Resultsmentioning

confidence: 99%

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

Hattinger¹,

Vella²,

Tavanti³

et al. 2016

Pharmacogenomics

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Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on different approaches and chemotherapy protocols, which are not yet standardized. Although several drugs have been used in HGOS second-line protocols, none of them has provided fully satisfactory results and the role of rescue chemotherapy is not well defined yet. This article focuses on the drugs that have most frequently been used for second-line treatment of HGOS, highlighting the present knowledge on their mechanisms of action and resistance and on gene polymorphisms with possible impact on treatment sensitivity or toxicity. In the near future, validation of the so far identified candidate genetic biomarkers may constitute the basis for tailoring treatment by taking the patients' genetic background into account. Osteosarcoma is the most common tumor of bone, which can exibit different levels of malignancy [1,2]. High-grade osteo sarcoma (HGOS) is a very aggressive neoplasm that, in unselected populations, is responsible for death of approximately 40-50% of patients [2,3]. The subgroup of the so-called conventional HGOS includes patients with high-grade tumors located in the extremities, nonmetastatic at diagnosis and younger than 40 years [1]. In this subgroup of HGOS, prognosis is slightly better, reaching 60-65% when patients are treated with multiagent neoadjuvant chemotherapy [4][5][6].The major clinical problem limiting the cure rate of HGOS patients is relapse, which in most cases consists in development of lung metastasis within the first 24-36 months from diagnosis [7,8]. Treatment of relapsed HGOS is based on different approaches and second-line chemotherapy protocols which, however, are not standardized and can rescue no more than 20-25% of patients [4,5]. Methods of data searching & selectionA systematic literature search was performed using 'treatment' and 'osteosarcoma' as key words in PubMed [9]. We further restricted the selection to studies performed in humans. By using all the aforementioned different combinations and selections, the literature searches revealed a total of 13,976 results. The key terms 'polymorphism', 'toxicity', 'drug response', 'drug resistance', 'pharmaco genetic', 'pharmacogenomic', 'epigenetic', 'methylation' and 'clinical trial' were then used to refine the results of the previous search, in order to select the publications which were strictly related to each section of this review. Full-length articles and reviews in English were taken into consideration.Only drugs used in at least two different clinical trials with published results were included in this review and, consequently, we considered genes and gene poly morphisms with possible relevance for response and/or

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Survival after recurrent osteosarcoma: Data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials

Cited by 118 publications

References 15 publications

Rare occurrence of bilateral breast and peritoneal metastases from osteogenic sarcoma

Rare occurrence of bilateral breast and peritoneal metastases from osteogenic sarcoma

Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma cells

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

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