Preface

The predecessor to this edition was titled *Osteosarcoma: Biology, Behavior, and Mechanisms*, and was the brainchild of my good friend Dr. Kurt Weiss and colleague Dr. Kanya Honoki. They sought to draw attention and enthusiasm to the recent advances in basic and clinical science research pertaining to osteosarcoma. There had been a relative stagnation in clinical advances over past decades in this rare cancer in comparison to other oncologic diseases. We began to understand the molecular biology and genetics of osteosarcoma but were unable to translate this into longer survival or improved prognosis. However, this was on the precipice of change with recent technological developments in big data genomics, improved understanding of molecular pathways, and discovery of new methods of epigenetic tumor regulation.

This edition is titled *Osteosarcoma—Diagnosis, Mechanisms, and Translational Developments*, and focuses on recent advancements and novel ideas in osteosarcoma research. In a manner of speaking, we have taken the multidisciplinary mindset essential for treating osteosarcoma and broadened it to include other areas of cancer research. By learning from gains in other areas of oncology, such as new lncRNAs, the understanding of cancer metabolism and oxidative phosphorylation, and new chemotherapy agents, we can apply them to the niche of osteosarcoma for treatment development. By drawing more attention to these novel and clever discoveries, we hope to continue this enthusiasm for advancements in basic and translational research in the field of osteosarcoma.

#### **Matthew Gregory Cable, MD**

Assistant Professor, Louisiana State University Health Sciences Center, Department of Orthopaedic Surgery, Division of Musculoskeletal Oncology, New Orleans, USA

### **Robert Lawrence Randall**

University of California, USA

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

**1. Introduction**

osteosarcoma.

sarcoma [7].

Introductory Chapter:

*Scott Barnett and Matthew G. Cable*

Integrating Basic Science with

Primary bone neoplasms are relatively uncommon. Among these tumors, osteosarcoma is the most common bone sarcoma, comprising approximately 35% of all malignant bone tumors [1]. Osteosarcoma affects approximately 500 children and adolescents annually in the United States with incidence peaking in the second decade of life during periods of rapid bone turnover and growth spurts [2]. Osteosarcoma arises from sites of rapid bone turnover, making the distal femur,

Although a genetic predisposition with mutations in various tumor-suppressor genes incurs a higher likelihood of developing osteosarcoma, most cases of osteosarcoma are sporadic. These chromosomal abnormalities yield defects in proteins involved in cell cycle regulation, resulting in uncontrolled cell proliferation [4]. These mutations are seen in a variety of disorders including Li-Fraumeni syndrome, which involves the p53 gene, or retinoblastoma, which involves the RB1 gene [5]. Some existing bone diseases such as Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostosis in addition to environmental risk factors, including radiation, have been identified as contributors to developing

Osteosarcoma serves as a broad term used to envelop the several different types of osteosarcoma that exist. These subtypes distinguish themselves through both clinical appearance as well as behavior. Unfortunately, the histological pictures of bone tumors do not definitively differentiate between osteogenic sarcoma, benign tumors, or other malignancies of bone [6]. Therefore, incorporation of both radiological and clinical tools is required to make the final diagnosis of osteogenic

In the setting of osteosarcoma, advanced imaging is warranted to evaluate the extent of tumor invasion, neurovascular involvement, bone marrow replacement, and presence of discontinuous metastases. Combination of MRI and CT imaging are helpful in demonstrating both soft tissue parameters of the tumor as well as cortical integrity and the presence of pathologic fracture [8, 9]. New focus on advanced techniques in medical image processing for the detection and analysis of osteosarcoma aims to better evaluate tumor locations, size, infiltrations of surrounding tissues, and identify the presence of satellite metastasis. Current research work utilizes positron emission tomography (PET) combined with MRI volumetry to better assess histological responses in bone sarcoma afflicted individuals, yielding

a Multidisciplinary Clinical

Approach for Osteosarcoma

proximal tibia and proximal humerus the most typical locations [3].

## **Chapter 1**
