Primary Bone -- Clinical Research Program

Our primary bone cancer team conducts research not only on cancers of the bone, but also on benign bone tumors and other cancer-like diseases that arise in or affect bone and the adjacent soft tissue. Our research group consists of surgeons, radiation oncologists, medical and pediatric oncologists, radiologists, and pathologists.

Among our accomplishments, we have been at the forefront of developing limb-salvaging surgery for patients with high-grade bone sarcomas. We also have led studies to create longer-lasting and more functional prostheses, including bone and joint replacements for children that grow as the child grows. Induction chemotherapy given before surgery was pioneered by our researchers, and our team is also investigating novel antineoplastic, antiangiogenic, metabolic, and radiation therapies.

Among our recent research accomplishments:

Detection, Diagnosis, and Prognosis

  • We found that gene expression signatures of osteogenic sarcomas identify alterations in specific genes that correlate with metastasis and poor prognosis. Cancer Res 2005;65:1748-1754. [PubMed Abstract]
  • Our imaging specialists are investigating the efficacy of dynamic contrast-enhanced MRI and magnetic resonance spectroscopy as an a priori predictor or early marker of tumor response. In bone sarcoma, the hypothesis is that magnetic resonance imaging technologies can identify lack of response early enough to allow effective change in chemotherapy. Early results suggest a promising correlation with pathology and that pretreatment ATP levels (perhaps a surrogate of hypoxia) in the soft-tissue components of bone sarcomas predict outcome. We are currently trying to broaden applicability by focusing on detecting lactate, which would allow extension of the studies to smaller soft-tissue components.
  • In patients with osteogenic sarcoma, we found that expression of the WNT family member LRP5 correlates with the presence of metastases and shorter time to progression, while absence of detectable telomere maintenance mechanisms favorably influences the course. This latter observation was followed up by mechanistic studies providing evidence for a possible role of Wnt signaling in the pathobiology and progression of osteogenic sarcoma.

Novel Therapeutic Approaches

  • Our investigators are leading national efforts evaluating new treatments for bone sarcomas. We have also developed an algorithm to manage local recurrence based on time to recurrence and the presence of metastases. We are leading a new clinical trial to assess the bisphosphonate pamidronate as both an antineoplastic and bone-protective agent; the rationale comes from preclinical and clinical studies of bisphosphonates in other cancers and from our identification of genes of the osteoclastic pathways as being highly upregulated. A large cooperative study in osteogenic sarcoma showed an interaction between the biologic agent muramyl tripeptide and ifosfamide treatment; the two agents appeared most effective in combination, but the interaction will need further study to untangle an unexpected interaction between them. The intensive P6 protocol resulted in a high event-free survival rate (82 percent at four years) for those with locoregional disease and large primary tumors at diagnosis, but three of the patients developed secondary malignancies. Cancer 2006;107:1607-1616. [PubMed Abstract]; J Clin Oncol 2005;23:2004-2011. [PubMed Abstract]
  • The outcome of prosthetic, bone, and soft-tissue reconstruction is a major focus of new work. Our surgeons have invented and patented an antiresorptive bone cement and completed a clinical trial in dog hip replacement. A novel method to improve prosthetic fixation to bone and prevent the stress bypass effect was proven effective in a clinical trial co-directed at Memorial Sloan Kettering, leading to FDA approval of the Compress knee replacement in 2005. Clinical evaluation of other implants is ongoing. We are also seeking functional improvement of transplanted allograft bone using mathematical modeling and testing in vitro and in vivo; the goal is prevention of graft resorption and fracture by optimizing the distribution of bisphosphonates in bone. J Biomechanics 2006;39:833-843. [PubMed Abstract]; J Bone Joint Surg Br 2005;87:1658-1662. [PubMed Abstract]