Vol 6, Issue 1 Feb 2016

Case Management: Orthopedic Treatment of Pediatric Osteosarcoma

Contributing Authors: Todd Bertrand, MD, MBA, Daniel L. Wurtz, MD

ACCREDITATION STATEMENT

Indiana University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians

DESIGNATION STATEMENT

Indiana University School of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity

FACULTY DISCLOSURE STATEMENT

Indiana University School of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity

COMMITTEE AND AUTHOR DISCLOSURE

Statements of Disclosure of Relevant Financial Relationships have been obtained from Todd Bertrand, MD and L. Daniel Wurtz, MD. Both Dr. Bertrand and Dr. Wurtz have disclosed that they have no relevant financial relationships with any commercial interests. in the field.

OBJECTIVES

Summarize the epidemiology and typical presentation of osteosarcoma

• Discuss the roles of neoadjuvant and adjuvant chemotherapy in the treatment of osteosarcoma.

• Describe the options for the surgical management of osteosarcoma.

• Compare the use of standard versus expandable endoprostheses for limb reconstruction in pediatric patients with osteosarcoma.



A 10-year-old girl is seen by her primary care physician for right knee pain of three months duration. A plain radiograph shows a concerning lesion around the right distal femur (Figure 1 see page 2), and she is referred to orthopedic oncology at Indiana University Health for evaluation. A biopsy reveals high-grade osteosarcoma. Staging studies, including a radionuclide bone scan and computed tomography (CT) of the chest, are performed and show no evidence of metastatic disease.

Overview of Pediatric Osteosarcoma

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Approximately 800 new cases are diagnosed annually in the United States,1 with 45 percent occurring in patients under the age of 16, and 17 percent in those younger than 12 years at diagnosis.2 Believed to arise from primitive osteoblastic cells, osteosarcomas can develop in any bone but have a predilection for the metaphyseal regions of the long bones of the extremities. The femur is the most common site for osteosarcoma formation, accounting for 42 percent of all cases, three-quarters of which are located in the distal femur (Table 1).3 Symptoms, predominantly pain occurring with or without activity, may be present for weeks to months or occasionally longer. Treatment and prognosis depend upon tumor staging (Table 2).

Medical Care

Before the introduction of chemotherapy in the 1970s, osteosarcoma was treated with surgical resection, usually amputation, and the results were dismal. While surgery provided good local disease control, more than 80 percent of patients developed metastatic disease, usually pulmonary in nature, within six months and died from their disease. The inescapable conclusion was that the majority of these individuals had subclinical metastases or micrometastatic disease at the time of diagnosis that were undetectable by techniques then available.4

The neoadjuvant and adjuvant use of chemotherapy was critical to improving outcomes in patients with osteosarcoma, according to Todd Bertrand, MD, assistant professor of orthopedic surgery at Indiana University School of Medicine. The inclusion of neoadjuvant (preoperative) chemotherapy not only systemically treats the individual, but it also allows further prognostic assessment. Patients with a good histopathologic response to neoadjuvant chemotherapy (>90 percent tumor cell necrosis) tend to have a better prognosis than those whose tumors fail to respond favorably.5

The chemotherapeutic drugs most active in osteosarcoma are doxorubicin, cisplatin, and high-dose methotrexate. Results from a Children’s Oncology Group clinical trial found that the addition of ifosfamide, a standard chemotherapeutic treatment for metastatic and non-metastatic soft tissue sarcoma, was not helpful. Radiation therapy is not usually a component of osteosarcoma care.6

The inclusion of neoadjuvant (preoperative) chemotherapy not only systemically treats the individual, but it also allows further prognostic assessment.

The patient undergoes four cycles of neoadjuvant chemotherapy with doxorubicin, cisplatin, and high-dose methotrexate. Magnetic resonance imaging performed at the completion of medical treatment shows a reduction in size of the extraosseous soft tissue mass associated with the tumor. A radionuclide bone scan and chest CT show no evidence of metastatic disease. To reduce the risk for perioperative complications, surgery is scheduled when her blood counts returned to normal.

Surgical Management

“Surgery is a component of all curative therapy for osteosarcoma,” reports Dr. Bertrand. “The speci c surgical procedure is dictated by the location and extent of the primary tumor, and the optimal reconstruction technique for young patients remains controversial. However, the majority of patients with extremity osteosarcomas are considered candidates for limb preservation operations.

“Provided tumor resection is anatomically possible and a wide negative margin can be obtained, limb preservation may improve functional outcome, quality of life, emotional health, and social functioning without sacricing local disease control,” Dr. Bertrand continues. “Recurrence rates following limb preservation range from five to 10 percent, and the five-year survival rate is approximately 70 to 75 percent in patients without metastatic disease.”7

Expandable Endoprostheses

Use of standard endoprostheses for limb reconstruction in pediatric patients can lead to limb-length inequality at skeletal maturity that adversely affects function. Nearly 70 percent of lower limb growth, for example, occurs at the distal femur and proximal tibia. Expandable endoprosthetic replacements allow for the reconstructed extremity to keep pace with the growth of the contralateral limb. These devices have differing expansion mechanisms but are usually comprised of two main parts: a stem, which generally contains the elongating system, and an articulation (Figure 2).

“Elongation of first-generation expandable endoprostheses required that the device be fully exposed during surgery, with the patient under general anesthesia,” reports Dr. Bertrand. “Today, these devices are lengthened via a minimally invasive operative procedure or noninvasively in the of ce setting using an electromagnetic device (Figure 3).”

The frequency of limb-lengthening is determined by periodic radiographs of the contralateral limb. Dr. Bertrand says that most patients tolerate between a 1.0 and 2.0 cm limb length discrepancy before lengthening becomes necessary. Mean lengthening achieved with an expandable distal femur endoprosthesis varies depending upon the size of the prosthesis and ranges from 2.0 to 13.0 cm, according to a retrospective review of implants from three manufacturers (Stryker, Biomet, and Stanmore).8

Complications are common following lower limb preservation surgery in children, with rates of 38 to 48 percent reported in the literature.8,9 The most frequent surgical complications are infection, including deep infection,and arthrofibrosis of the knee.8,10 Aseptic loosening and implant mechanical failure are the major problems affecting implant longevity.

Surgery takes place two weeks after the completion of neoadjuvant chemotherapy. After careful dissection to fully expose the tumor and any soft tissue extension, the tumor is resected. A distal femoral bone marrow margin is sent to pathology for frozen section, which is negative for osteosarcoma. The proximal tibia is prepared, trial components inserted, and the Biomet Compress device (Figure 4) is secured to the remaining distal femur. Next, trial femoral components are inserted, and the knee is reconnected via a hinge mechanism. After limb length and rotation are established, the trial components are removed and the final components placed. The incision is closed in standard fashion over suction drains.

The patient is taken from the operating room to recovery and subsequently transferred to a regular post-surgical floor. She receives inpatient physical therapy and is discharged on postoperative day 3 in good condition.

Two weeks after surgery, the patient begins postoperative chemotherapy with the same three-drug regimen used neoadjuvantly. Treatment is continued for four months, after which the patient is monitored on a routine basis with radiographs, chest CT, and radionuclide bone scans.

Over the next several years until skeletal maturity, the patient undergoes progressive lengthening of the prosthesis without complications. Nine years postoperatively, she has no evidence of recurrent or metastatic disease, and her prosthesis is functioning well without a clinically noticeable discrepancy in leg length (Figure 5).

Outcomes

The advent of adjuvant chemotherapy for osteosarcoma in the 1970s dramatically reduced the incidence of metastatic disease and increased survival. However, patients who present with metastases at diagnosis still have poor five-year survival rates of 20 to 30 percent.11 While surgical techniques and prosthetic implants have improved over the last 35 years, outcomes have remained relatively unchanged since the introduction of chemotherapy.12

“Osteosarcomas likely represent a diverse group of tumors, each with its own unique genetic footprint (see Advanced Praxis, December 2015),” concludes Dr. Bertrand. “There is still much to be understood at a molecular level to advance the treatment of these still too often fatal tumors.”

Todd Bertrand, MD, MBA

Orthopedic Surgeon, IU Health Assistant Professor of Orthopedic Surgery
Indiana University School of Medicine
tbertrand@iuhealth.org

Dr. Bertrand received his medical degree from IU School of Medicine, did his residency in orthopedic surgery at Duke University Medical Center in Durham, NC, completed a fellowship in musculoskeletal oncology at the H. Lee Mof tt Cancer Center and Research Institute in Tampa, FL, and did additional training at the Rizzoli Orthopedic Institute in Bologna, Italy.

Dr. Bertrand’s research focuses on bone and soft tissue sarcomas. He is the author of several peer-reviewed publications and has presented at professional meetings in the United States.

Daniel L. Wurtz, MD

Co-Service Line Leader, IU Health Physcians Orthopedics & Sports Medicine Interim Chairman of Orthopedic Surgery
Indiana University School of Medicine
dwurtz@iuhealth.org

Dr. Wurtz received his medical degree from the University of South Alabama in Mobile, did his residency in orthopedic surgery at Wilford Hall US Air Force Medical Center in San Antonio, TX, and completed a fellowship in musculoskeletal oncology at the University of Chicago, IL.

A recipient of the Command Flight Surgeon of the Year award and the Air Force Commendation medal, Dr. Wurtz has twice received the IU Trustees Teaching Award. He is the author of more than one dozen peer-reviewed publications and has presented at numerous professional meetings in the United States.

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