Management of Bone Sarcoma a b c,d, Christina J. Gutowski, MD , Atrayee Basu-Mallick, MD , John A. Abraham, MD * KEYWORDS Bone sarcoma Osteosarcoma Ewing sarcoma Chondrosarcoma Endoprosthetic reconstruction KEY POINTS Advancements in chemotherapy have been the primary reason for improvements in sur- vival from bone sarcoma in the past 20 years. There are currently no chemotherapy agents effective against conventional chondrosarcoma. Local recurrence of bone sarcoma is likely related to aggressive tumor biology, but rela- tionship with survival is not fully understood. Multiple methods of reconstruction after bone sarcoma resection are available, each with its own benefits and drawbacks. Emerging technologies, such as computer-aided surgery, improved imaging, and improved implant design, have potential to improve results of treatment even further in the future. INTRODUCTION Incidence and Epidemiology Bone sarcomas account for approximately 0.2% of new cancer cases in the United States each year. The vast majority of these are either osteosarcoma, Ewing sarcoma, or chondrosarcoma. In 2016, it is estimated that 3300 new cases will be diagnosed; this incidence has been rising on average 0.4% annually over the past decade.1 More than 27% of new diagnoses are made in patients younger than 20 years; osteosarcoma spe- cifically is reported to be the third most common cancer in adolescence, and eighth We have no funding sources, or commercial/financial conflicts of interest to disclose. a Department of Orthopedic Surgery, Sidney Kimmel Medical College at Thomas Jefferson Uni- versity, 1025 Walnut Street, Room 516 College, Philadelphia, PA 19107, USA; b Department of Medical Oncology, Sarcoma and Bone Tumor Center at Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 700, Philadelphia, PA 19107; c Department of Orthopedic Surgery, Rothman Institute at Jefferson University Hospital, 925 Chestnut Street, Philadelphia, PA 19107, USA; d Department of Surgical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA * Corresponding author. E-mail address: [email protected] Surg Clin N Am 96 (2016) 1077–1106 http://dx.doi.org/10.1016/j.suc.2016.06.002 surgical.theclinics.com 0039-6109/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved. 1078 Gutowski et al most common cancer in children overall.2 Unlike osteosarcoma and Ewing sarcoma, which peak in adolescent age groups, chondrosarcoma incidence increases with age.3 It is estimated that 1490 patients will die of bone sarcoma in 2016, representing 0.3% of all cancer deaths.1 For osteosarcoma, the implementation of multimodal treatment with chemotherapy and surgery has led to a considerable improvement in overall survival, but since that time, survival rates have remained relatively stable. In 2015, cause-specific 10-year survival for patients with localized disease at the time of osteosarcoma diagnosis was 65.8%.4 Metastatic disease at presentation, which is seen in approximately 24% of patients, lowers this survival rate to 24%.4,5 Despite improvement in survival of localized disease with modern management, patients with recurrence or metastasis after initial treatment is still associated with a poor prognosis. Pretreatment Evaluation and Staging The goal of the preoperative evaluation is to determine the extent of the disease, and allow for optimum treatment planning. Local imaging usually includes orthogonal plain radiographs and MRI of the affected area (Figs. 1 and 2). Computed tomography (CT) scan may be helpful in identifying cortical involvement. Imaging of the entire affected bone should be included to identify any skip metastases, the presence of which worsens prognosis.6 Evaluation of distant disease is done by using chest CT scan to evaluate for pulmo- nary metastasis, and Technicium-99 whole-body bone scan and/or PET with fludeox- yglucose F 18 (F18-FDG PET)/CT to evaluate for bony metastases7,8 (Fig. 3). Recent studies have demonstrated that PET/CT is more sensitive than bone scan for detect- ing metastatic bone lesions, while specificity and diagnostic accuracy were similar. The combination of bone scan and PET/CT provides the highest sensitivity, specificity, and diagnostic accuracy, but this must be balanced with the additional cost. PET/CT scan may have the additional benefit of demonstrating correlation with the aggressive- ness of a bone lesion, although is not completely reliable for this purpose.9,10 Once biopsy is completed, various staging systems exist. The American Joint Com- mittee on Cancer (AJCC) is most commonly used. For bone sarcoma specifically, an alternative system frequently used is the Musculoskeletal Tumor Society (MSTS) sys- tem, described by Enneking in 198011 (Tables 1 and 2). Biopsy When performed appropriately, diagnostic accuracy of surgical incisional biopsy has been shown to be 98%,12 and as such, surgical biopsy is the preferred method of Fig. 1. Orthogonal radiographs and coronal short tau inversion recovery (STIR) MRI scan of conventional osteosarcoma of the right distal femur. Management of Bone Sarcoma 1079 Fig. 2. Anteroposterior radiograph and coronal STIR MRI scan of chondrosarcoma of the left proximal femur. obtaining tissue by most surgical pathologists. However, from a technical standpoint, open biopsy is associated with a complication rate of 16% and therefore must be per- formed by an experienced center. Mankin and colleagues13,14 demonstrated that biopsy-related problems occurred with 3 to 5 times greater frequency at centers inex- perienced with sarcoma treatment, when compared with sarcoma treatment centers. Several principles to minimize risk of contamination and complication while maintain- ing adequate yield and accuracy have been described (Box 1). Currently, percuta- neous needle biopsy has replaced open surgical biopsy in most experienced centers as the primary method of biopsy due to low complication rate and a high level Fig. 3. Technicium-99 whole-body bone scan of patient with localized osteosarcoma of the right distal femur. 1080 Gutowski et al Table 1 American Joint Committee on Cancer staging system for bone sarcomas Stage Tumor Size Lymph Involvement Grade IA <8 cm No lymph node involvement or metastasis Low IB 8 cm No lymph node involvement or metastasis Low IIA <8 cm No lymph node involvement or metastasis High IIB >8 cm No lymph node involvement or metastasis High III Skip metastasis No lymph node involvement or metastasis Any IVA Any size No lymph node involvement, metastasis to the lung Any IVB Any size Any lymph node involvement or any metastasis to site Any other than the lung Adapted from Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer, 2010. of accuracy, but relies heavily on the acumen of the bone pathologist given the low yield of tissue from this procedure. Percutaneous needle biopsy With complication rates of approximately 1%, percutaneous needle biopsy with or without image guidance represents a safe, cost-effective, minimally invasive alterna- tive to surgical biopsy.16–19 Diagnostic accuracy rates range from 74% to 93% when imaging modalities are used.19–21 Major disadvantages of needle biopsies, in general, relate to the small amount of tissue obtained, and the potential for sampling error. For these reasons, fine needle aspirate (FNA) is usually insufficient for primary bone sarcoma. However, core needle biopsy (CNB) has consistently been shown to facili- tate accurate histopathologic interpretation and achieve favorable patient out- comes.17,19,22 The difference in hospital charges associated with percutaneous biopsies and open biopsies was found to be approximately $6000.23 Furthermore, recent data suggest that seeding of the needle biopsy tract may not occur as it does in open surgical biopsy.24 Many studies have attempted to identify risk factors for poor diagnostic capability or patient outcome after CNB. Increased sensitivity, diagnostic accuracy, and ability to differentiate between benign and malignant lesions are seen in needle biopsy of bone sarcomas compared with soft tissue sarcomas.17,21,23 In general, malignant bone tumors are associated with higher diagnostic yield than benign lesions.24,25 Biopsies of necrotic areas of a tumor are likely to produce nondiagnostic tissue, so im- age guidance is critical in determining the optimal target of the biopsy needle. Highly Table 2 Musculoskeletal Tumor Society staging system for bone sarcomas Stage Grade Site IA Low Intracompartmental IB Low Extracompartmental IIA High Intracompartmental IIB High Extracompartmental III Any regional/distal metastases Any From Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop 1980;153:106–20. Management of Bone Sarcoma 1081 Box 1 Principles of safe and effective surgical biopsy of musculoskeletal lesions Principles of surgical biopsy Plan the biopsy as carefully as the definitive resection procedure Carry out procedure with minimal contamination of normal tissues Drain tract must be clearly marked and close to and in line with surgical biopsy incision, to be resected at definitive procedure Pay careful attention to antiseptic technique, skin sterilization, hemostasis, and wound closure Avoid transverse incisions, and place skin incision in such a matter so as to not compromise subsequent definitive surgery Ensure adequate amount of representative tissue is obtained, communicate confirmation with pathologist