Benefits and Adverse Events in Younger Versus Older Patients Receiving Neoadjuvant Chemotherapy for Osteosarcoma: Findings From a Meta-Analysis

Collins, Marnie; Wilhelm, Miriam; Conyers, Rachel; Herschtal, Alan; Whelan, Jeremy; Bielack, Stefan; Kager, Leo; Kühne, Thomas; Sydes, Matthew R.; Gelderblom, Hans; Ferrari, Stefano; Picci, Piero; Smeland, S.; Eriksson, Mikael; Petrilli, Antônio Sérgio; Bleyer, Archie; Thomas, David M.

doi:10.1200/jco.2012.43.8598

Cited by 154 publications

(136 citation statements)

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“…1 Use of chemotherapy along with surgery has raised the long-term survival rate of osteosarcoma patients to approximately 70%. 2,3 Doxorubicin, cisplatin, and methotrexate are commonly used chemotherapeutics active against osteosarcoma. In particular, cisplatin is the most widely used platinum-based anticancer drug for solid tumors including osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

et al. 2016

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Recent progress in chemotherapy has significantly increased its efficacy, yet the development of chemoresistance remains a major drawback. In this study, we show that GFRA1/GFRa1 (GDNF family receptor a 1), contributes to cisplatin-induced chemoresistance by regulating autophagy in osteosarcoma. We demonstrate that cisplatin treatment induced GFRA1 expression in human osteosarcoma cells. Induction of GFRA1 expression reduced cisplatin-induced apoptotic cell death and it significantly increased osteosarcoma cell survival via autophagy. GFRA1 regulates AMPK-dependent autophagy by promoting SRC phosphorylation independent of proto-oncogene RET kinase. Cisplatin-resistant osteosarcoma cells showed NFKB1/NFkB-mediated GFRA1 expression. GFRA1 expression promoted tumor formation and growth in mouse xenograft models and inhibition of autophagy in a GFRA1-expressing xenograft mouse model during cisplatin treatment effectively reduced tumor growth and increased survival. In cisplatin-treated patients, treatment period and metastatic status were associated with GFRA1-mediated autophagy. These findings suggest that GFRA1-mediated autophagy is a promising novel target for overcoming cisplatin resistance in osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

et al. 2016

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“…In the 50% of patients whose tumors respond 'poorly' to neoadjuvant therapy and who have a poor outcome with survival rates of about 50% [3], pharmacogenomic investigations might focus on the identification of novel therapeutic targets. Indeed, recent insights from NGS analyses identified the PI3K/mTOR pathway as a promising therapeutic target [14].…”

Section: Expert Opinionmentioning

confidence: 99%

“…At definitive surgery, 50% of patients had < 10% tumour viability (i.e., good response) in the resected specimens [2]. Response to neoadjuvant chemotherapy is an important prognostic factor, and patients whose tumors responding well to preoperative therapy can achieve longterm overall survival rates of about 80% [3]. Based upon their exciting results in a small cohort of patients whose tumors had responded poorly to neoadjuvant chemotherapy, Rosen et al had hypothesized back in 1982 that altering postoperative chemotherapy (i.e., intensification) should improve outcomes in such patients.…”

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confidence: 99%

“…Variation in drug effects result from the interplay of many variables, including for example, age, sex, ethnicity, nutritional status, renal and liver function, concomitant illnesses, other medications and genetics. In HGOS, for example, age and sex have been identified as independent prognostic variables, and children and females have obtained better outcomes than older patients and males, respectively [3].…”

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confidence: 99%

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Can pharmacogenomics help to improve therapy in patients with high-grade osteosarcoma?

Kager

Diakos

Bielack

2015

Expert Opinion on Drug Metabolism & Toxicology

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“…6 It is worth mentioning that chemotherapy has toxicity that may result in death. 7 This aspect needs to be taken into consideration in therapeutic planning.…”

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confidence: 99%

Primary osteosarcoma of the breast: pathological and imaging findings

Conde¹,

Morais²,

Pacheco³

et al. 2015

Rev. Assoc. Med. Bras.

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Financial support: none suMMary Primary osteosarcoma of the breast (POB) is an extremely rare and aggressive tumor. Differential diagnosis of POB includes osteosarcoma of the chest wall and metaplastic breast carcinoma. Imaging tests that exclude the existence of a direct connection between the tumor and chest wall, as well as histopathological and immunohistochemical studies that rule out the presence of an epithelial component are required for the diagnosis of POB. We report a case of a 69-year old woman with POB. Imaging and pathological findings are presented. Therapeutic approach is discussed in the light of current knowledge, including potential complications.Keywords: breast, breast neoplasms, sarcoma, immunochemistry.A 69-year-old woman presented with a 6-month history of a palpable, painless mass in her left breast. Clinical examination revealed a hard, mobile, well-circumscribed, 10 cm mass, occupying practically the entire left breast. Contralateral breast, axilla or nipples showed no abnormalities. She denied having any history of breast trauma, radiotherapy, or breast cancer.Mammography revealed a relatively well-defined, hyperdense irregular mass without calcifications, unconnected to the underlying sternum and ribs ( Figure 1A). Ultrasound revealed a hypoechoic irregular mass with hyperechoic areas, indistinct margins, and posterior acoustic shadowing ( Figure 1B). Core needle biopsy was performed and microscopy showed a malignant poorly differentiated mesenchymal tumor.Thoracic and abdominal computed tomography showed no distant metastasis. The patient underwent simple mastectomy and sentinel lymph node biopsy. Grossly, the cut surface of the tumor was white, hard, with a stony consistency in the center and well-defined margins. The tumor measured 10x9x7 cm (Figure 2).Microscopy showed a malignant immature mesenchymal bone-forming tumor. There were foci of necrosis and cartilage, containing osteoid matrix, some of which were irregularly calcified, surrounded by atypical spindle cells and osteoclast-like multinucleated giant cells. Tumor mitotic count was 16 mitoses/10 high-power field. There was no skin and lymphovascular invasion. Sentinel lymph node was tumor-free. On immunohistochemistry, tumor cells were positive for vimentin. CD68 (KP1) and alpha-1-antitrypsin were positive in osteoclast-like giant cells. Cytokeratin (AE1/AE3), S-100, epithelial membrane antigen (EMA), p63, epidermal growth factor receptor (EGFR), CD99, estrogen and progesterone receptors, and HER2 were negative. The Ki-67 index was 5%. Extensive tumor sampling failed to identify any tumor that was biphasic or had epithelial component. A highgrade primary osteosarcoma of the breast (POB) was di-

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Benefits and Adverse Events in Younger Versus Older Patients Receiving Neoadjuvant Chemotherapy for Osteosarcoma: Findings From a Meta-Analysis

Abstract: These results suggest fundamental differences in the way chemotherapy is handled by females compared with males and by children compared with older populations. These differences may influence survival in a disease in which chemotherapy is critical to overall outcomes.

Cited by 154 publications

References 45 publications

GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

Can pharmacogenomics help to improve therapy in patients with high-grade osteosarcoma?

Primary osteosarcoma of the breast: pathological and imaging findings

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