Osteosarcoma: A Case Study in Why Multidisciplinary Collaboration Matters

A Second Chance: “My quality of life and health are as great as they were before surgery, if not better. I am able to be just as active and enjoy working out, swimming, bike riding, and anything from sand volleyball to golf to jumping on a trampoline. I have nearly no limitations.”

The above quote is from a patient whose world was rocked in 2006 when he was told, at age 15, that his progressively growing tibial mass had imaging and biopsy findings consistent with a high-grade nonmetastatic osteosarcoma (Figure 1).

Figure 1. Anteroposterior radiograph (left) and MRI (right) showing the bone destruction and soft-tissue mass (arrows) of an aggressive osteosarcoma of the proximal tibia at the time of diagnosis in the 15-year-old case patient

Rather than allowing the news to end his career hopes and life aspirations, this young man teamed with specialists in Cleveland Clinic’s multidisciplinary Musculoskeletal Tumor Center to treat the high-grade bone sarcoma. The overall treatment strategy combined a multiagent chemotherapy regimen with an allograft-prosthetic composite reconstruction of the proximal tibia-fibula, augmenting the extensor mechanism using a medial gastrocnemius flap (Figure 2).

Figure 2. Anteroposterior (left) and lateral (right) radiographs showing the case patient’s allograft-prosthetic composite placed after chemotherapy and resection with a negative margin.

Six years later, this patient is now thriving as a 21-year-old University of Toledo student who is focused on his goal of becoming a nurse. He remains free of metastases and is grateful for what he calls his “second chance” on life.

Dramatic Evolution in Treatment

One of the greatest paradigm shifts in bone and joint surgery in the past three decades has been in the treatment of primary sarcoma of the bone. In the 1960s and ’70s, the gold standard treatment of primary osteogenic sarcoma (osteosarcoma) of bone was rooted in limb amputation, with expected survivorship hovering at an abysmal 10 to 20 percent despite heroic surgical efforts to procure clear margins in an attempt to “cure” the body of the malignant process. Before the advent of complex imaging modalities, preoperative “mapping” of tumor margins was difficult, leading physicians to prioritize patient survivorship (amputation) over functional salvage.

With advances in adjuvant and neoadjuvant chemotherapy in the 1980s, accompanied by the advent of MRI and CT imaging, limb salvage procedures began to gain prominence without sacrificing survivorship. As these multidisciplinary approaches evolved, five-year survival curves began to show a significant rise, with current long-term survival rates in nonmetastatic osteosarcoma approaching 80 percent. Today, more than 80 percent of bone and soft-tissue sarcomas in the extremities are managed with surgical limb salvage.

Why Multidisciplinary Collaboration Is Critical

Osteosarcoma is the most common primary bone malignancy. The age at diagnosis follows a bimodal distribution, with most cases occurring between ages 12 and 25 or in the seventh decade of life. While no gender predilection is noted in earlier childhood, there is a shift toward male preponderance in late adolescence. The presence of metastases at diagnosis or at primary recurrence worsens prognosis, with 10-year survival rates of only 20 to 30 percent reported in patients with known metastases. Osteosarcoma subtype also correlates with prognosis, with less-aggressive subtypes such as parosteal osteosarcoma reported to have long-term survival rates generally greater than 90 percent.

Neoadjuvant (preoperative) and adjuvant (postoperative) chemotherapy have become a mainstay in osteosarcoma treatment. Neoadjuvant therapy serves to guide prognosis based on histological tumor necrosis response. It also aids the surgeon by preoperatively “maturing” (and, if possible, shrinking) the tumor margins to gain more accessible boundaries that allow for preservation of muscles and neurovascular tissues. Given the complexities of advances in adjuvant and neoadjuvant therapy for sarcoma, multidisciplinary collaboration becomes vital to most patients’ chances for optimal outcome. It is this philosophy of multidisciplinary care that invigorates Cleveland Clinic’s approach to musculoskeletal sarcoma treatment.

A Progressive Multidisciplinary Approach

At our Musculoskeletal Tumor Center, we partner with an experienced team of Cleveland Clinic pathologists, radiation oncologists and medical oncologists to target subtypes of bone and soft-tissue sarcomas with tailored advanced treatment regimens. For patients with adolescent osteosarcoma, our pediatric oncologists help oversee the medical treatments, orchestrating a 10-week neoadjuvant course of cisplatin, doxorubicin and high-dose methotrexate. At the completion of this therapy, a resection specimen is studied for tumor response, and the aforementioned course is continued for 30 weeks total if there is greater than 90 percent tumor necrosis. If a less-dramatic response is noted after the index 10 weeks (< 90 percent necrosis), then ifosfamide and etoposide can be added for a total therapy duration of 40 weeks. In addition, we are conducting randomized clinical trials at Cleveland Clinic to help ascertain the role of interferon-alpha following chemotherapy for reducing the risk of relapse.

After limb salvage surgery, patients are quickly integrated into an aggressive postoperative physical therapy regimen to aid with gait training, range-of-motion gains and strengthening goals. Long-term follow-up with the orthopaedic oncologist and medical oncologist ensures that the disease process is monitored closely, establishing a lifelong partnership between the patient and his or her team of physicians.

Optimal outcomes from bone and soft-tissue sarcomas are possible only with a coordinated, multidisciplinary approach that takes advantage of the most advanced medical and surgical therapies. At Cleveland Clinic, reconstructive options in limb salvage surgery, such as allograft-prosthetic composites, intercalary allografts and metallic endoprostheses, are supplemented with unique resources such as our active bone bank. Additionally, our use of preoperative three-dimensional imaging in consultation with our musculoskeletal radiologists helps to enhance preoperative planning of tumor resection margins.

Looking ahead, our hope is that trials such as our ongoing study of post-chemotherapy interferon-alpha therapy will allow us to continue making advances that both deepen understanding of the osteosarcoma disease process and help physician teams improve functionality and quality of life for patients like the young man with the “second chance” profiled here.

About the Authors

Dr. Mesko is a PGY-4 orthopaedic resident and Dr. David Joyce is a PGY-5 orthopaedic resident at Cleveland Clinic.

Dr. Michael Joyce specializes in trauma, oncology, total joint replacement and musculoskeletal tissue banking.

Dr. Lietman, Director of the Musculoskeletal Tumor Center, specializes in orthopaedic oncology and adult reconstruction.