McMaster University

McMaster University

An x-ray of a human knee showing signs of a bone sarcoma.

Musculoskeletal Tumor Surgery

Principal Investigators

A photo link to the bio of Dr. Michelle Ghert

Dr. Michelle Ghert

A photo link to the bio of Dr. Ben Deheshi

Dr. Ben Deheshi

Current Research Initiatives

PARITY

Metastatic Bone Disease Studies

Dr. Benjamin Deheshi’s studies on metastatic bone disease currently include a retrospective review and prospective study with an aim to develop a more robust, reliable, and practical methodology for identifying patients with metastatic bone disease who would benefit from prophylactic surgery. These studies will be pivotal as we enter into an era of medicine in which the expectations of patient management for those with terminal diseases often exceed established protocol.

Background

Malignant Bone Tumors

Malignant bone tumors (bone sarcomas) often affect adolescents and young adults. Care of patients with bone sarcomas is carried out in specialty centers, as these are rare forms of cancer. In Canada, bone sarcomas affect 4 to 5 patients per million persons each year. Long-bone sarcomas were historically managed with amputations, but the current standard is limb salvage surgery, which involves wide tumor resection followed by functional reconstruction. With the aid of modern imaging techniques and chemotherapeutic regimens, limb salvage is possible in 95% of patients. The most common type of functional reconstruction involves the use of tumor endoprostheses - modular metallic and polyethylene implants that replace surgically resected bones and joints.

Due to the complexity and length of musculoskeletal tumor surgeries, as well as the immunocompromised nature of patients treated with chemotherapy, the risk for deep post-operative infection remains high and the outcomes following infection can be devastating. These infections require staged endoprosthetic revision surgery and long-term intravenous antibiotic therapy. Even following this management, repeat infection and ultimate amputation are not uncommon. Up to 50% of these cases end in amputation. Patients’ function and quality of life are dramatically impacted, as are health care costs.

International Collaborative Trials

The rarity of sarcomas of the long bones dictates that multi-center international collaborations are essential in order to adequately power surgical trials in this field, but there is no precedent for such an undertaking in this field. The PARITY (Prophylactic Antibiotics in Tumor Surgery) trial is the first large-scale randomized surgical trial in Orthopaedic Oncology, and its rigorous design, organization, and execution will set a high benchmark for future research.

Outcomes Measurement

In large clinical trials, small treatment effects may frequently be “statistically significant” without demonstrating patient-important benefit that would warrant changes in management. Data collected in the PARITY trial will be used in a sub-study to estimate the “Minimal Important Differences” MIDs for commonly used musculoskeletal oncology functional outcome scores. These MIDs will clarify treatment effect sizes and enhance clinical decision-making, as well as provide a useful guide to sample size calculations for subsequent large trials. Ultimately, this work will enhance the methodological rigor of clinical investigation in Orthopedic Oncology and improve the outcomes of patients with primary bone sarcomas.

Metastatic Bone Disease

Of all the new cases of invasive cancers diagnosed each year, approximately 50% eventually metastasize to bones. Breast, prostate, lung, thyroid and renal cancer account for an estimated 42,600 new metastatic bone disease cases each year in Canada alone. Metastatic bone lesions predispose to pathological fracture, which exposes patients to extreme pain, urgent hospitalization, and the risks of surgery in less than ideal circumstances. High-risk lesions can be treated with radiation, drugs, or surgery. Predicting an impending fracture and performing prophylactic surgical fixation in an elective setting are critical to avoid debilitating complications, but current predictive scoring systems are limited. Our current studies aim to characterize the typical indicators for prophylactic fixation and develop a robust, reliable, and practical methodology for identifying patients with metastatic bone disease who would benefit from surgery.

The objectives of the Orthopaedic Oncology and sarcoma team are:

  • To establish the first international collaborative trials network in the field of orthopaedic oncology.
  • To determine the optimal dosing of antibiotics in patients undergoing limb salvage surgery.
  • To determine the Minimal Important Differences for the commonly used musculoskeletal tumor surgery functional outcome measures.
  • To develop a practical, reproducible, and accurate way to predict fracture risk for metastatic bone lesions.

Recent Publications

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  • Clin Orthop Relat Res. 2013 Oct 1. [Epub ahead of print] PubMed PMID: 24081669.

    What Are the Levels of Evidence on Which We Base Decisions for Surgical Management of Lower Extremity Bone Tumors?

  • Clin Orthop Relat Res. 2013 Jun;471(6):2017-27. PubMed PMID: 23404421; PubMed Central PMCID: PMC3706642.

    High infection rate outcomes in long-bone tumor surgery with endoprosthetic reconstruction in adults: a systematic review.

  • Curr Oncol. 2013 Jun;20(3):e247-54. PubMed PMID: 23737694; PubMed Central PMCID: PMC3671031.

    Sarcoma Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care. Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline.

  • Open Orthop J. 2013 May 3;7:109-13. PubMed PMID: 23730372; PubMed Central PMCID: PMC3664450.

    Expressional Analysis of GFP-Tagged Cells in an In Vivo Mouse Model of Giant Cell Tumor of Bone.

  • Open Orthop J. 2013 Apr 28;7:103-8. PubMed PMID: 23730371; PubMed Central PMCID: PMC3664443.

    A Systematic Review and Meta-Analysis of En-Bloc vs Intralesional Resection for Giant Cell Tumor of Bone of the Distal Radius.

  • J Orthop Res. 2013 Mar;31(3):493-501. PubMed PMID: 22968857.

    ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma

  • Rare Tumors. 2013 Feb 11;5(1):e2. PubMed PMID: 23772301; PubMed Central PMCID: PMC3682454.

    Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis.

  • Orthopedics. 2013 Feb;36(2):e216-22. PubMed PMID: 23380017.

    Use of a calcium sulfate-calcium phosphate synthetic bone graft composite in the surgical management of primary bone tumors.

  • BMJ Open. 2012 Nov 28;2(6). PubMed PMID: 23194956; PubMed Central PMCID: PMC3533099.

    Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study.

  • J Bone Miner Res. 2012 Sep;27(9):1976-91. PubMed PMID: 22508574.

    Transcriptomic and proteomic analyses in bone tumor cells: Deciphering parathyroid hormone-related protein regulation of the cell cycle and apoptosis

  • J Bone Joint Surg Am. 2012 Aug 1;94(15):1399-405.

    Effects of neoadjuvant chemotherapy on image-directed planning of surgical resection for distal femoral osteosarcoma.

  • BMC Musculoskelet Disord. 2012 Jun 7;13:91. PubMed PMID: 22676321; PubMed Central PMCID: PMC3461415.

    Prophylactic antibiotic regimens in tumor surgery (PARITY) survey.

  • J Orthop Res. 2012 Jun;30(6):877-84. PubMed PMID: 22102368.

    PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone.

  • Ann Surg Oncol. 2012 Apr;19(4):1081-8. PubMed PMID: 22052112

    Canadian Orthopaedic Oncology Society (CANOOS). Myxoid\round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases.

  • Biochem Biophys Res Commun. 2012 Mar 23;419(4):719-23. PubMed PMID: 22386994.

    T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone.

  • PLoS One. 2012;7(10):e46769. PubMed PMID: 23071632; PubMed Central PMCID: PMC3469652.

    Investigation of FGFR2-IIIC signaling via FGF-2 ligand for advancing GCT stromal cell differentiation.

  • J Cell Biochem. 2011 Sep;112(9):2287-95. PubMed PMID: 21503964.

    The role of TWIST as a regulator in giant cell tumor of bone.

  • J Bone Joint Surg Br. 2011 Aug;93(8):1093-7.

    Fixation of pathological humeral fractures by the cemented plate technique.

  • Ann Surg Oncol. 2011 Jun;18(6):1705-9. PubMed PMID: 21258968.

    A systematic review and meta-analysis of intralesional versus wide resection for intramedullary grade I chondrosarcoma of the extremities.

  • Ann Surg Oncol. 2010 May;17(5):1367-74. PubMed PMID: 20217260.

    A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma.

  • Sarcoma. 2010; PubMed PMID: 20706639;

    High-Speed Burring with and without the Use of Surgical Adjuvants in the Intralesional Management of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis.

  • Journal of Arthroplasty

    A biomechanical evaluation of press-fit stem constructs for tumor endoprosthetic reconstruction of the distal femur

  • Skeletal Radiology

    Intra-articular nodular fasciitis of the shoulder: A case report and review of the literature

  • The Annals of Surgical Oncology

    A systematic review and meta-analysis of intralesional versus wide resection for intramedullary grade I chondrosarcoma of the extremities

  • The Annals of Surgical Oncology

    Patient-oriented functional results of total femoral endoprosthetic reconstruction following oncologic resection

  • Clinical Imaging

    Radiology-pathology conference: cutaneous angiosarcoma of the leg

  • Bone

    Parathyroid hormone-related protein (PTHrP) modulates adhesion, migration and invasion in bone tumour cells

  • Bone

    Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

  • Clinical Orthopaedics and Related Research

    High infection rate outcomes in long-bone tumor surgery with endoprosthetic reconstruction in adults: a systematic review

  • Rare Tumors

    Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis

  • Current Oncology

    Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline

  • Current Oncology

    Lost in translation: animal models and clinical trials in cancer treatment

  • Journal of Knee Surgery

    Infrapatellar Fat Pad Osteochondroma: Three Cases and a Systematic Review

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