The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery

Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.

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Survival Analysis of 3 Different Age Groups and Prognostic Factors among 402 Patients with Skeletal High-Grade Osteosarcoma. Real World Data from a Single Tertiary Sarcoma Center

Cancers ◽

10.3390/cancers13030486 ◽

2021 ◽

Vol 13 (3) ◽

pp. 486

Author(s):

Richard E. Evenhuis ◽

Ibtissam Acem ◽

Anja J. Rueten-Budde ◽

Diederik S. A. Karis ◽

Marta Fiocco ◽

...

Keyword(s):

Prognostic Factors ◽

Medical Center ◽

Age Groups ◽

High Grade ◽

Real World Data ◽

Poor Overall Survival ◽

Histopathological Response ◽

Curative Intent ◽

Entire Cohort ◽

High Grade Osteosarcoma

Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics.

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Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽

10.3390/cancers13122878 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2878

Author(s):

Claudia Maria Hattinger ◽

Maria Pia Patrizio ◽

Leonardo Fantoni ◽

Chiara Casotti ◽

Chiara Riganti ◽

...

Keyword(s):

Drug Resistance ◽

Therapeutic Targets ◽

Treatment Strategies ◽

Cure Rate ◽

Acquired Drug Resistance ◽

Unselected Patient ◽

Dismal Prognosis ◽

Non Coding Rnas ◽

High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

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