Guide to trainees for the orthopaedic oncology rotation

We have compiled the following unofficial guide to trainees coming to the North of England Bone and Soft Tissue Tumour Service. It contains key topics in the curriculum to which you may get exposure in this attachment, competence levels for surgical procedures and other useful information.

Orthopaedic Oncology Syllabus

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Metastatic Bone Disease

Metastasis, or metastatic disease, is the spread of cancer from an initial or primary site in one organ or part of the body to a secondary non-adjacent organ or part.

Epidemiology

It is estimated that there are over 20,000 new cases of metastatic bone disease (MBD) in the UK each year.

Although any type of cancer can in theory spread to bone, MBD is most commonly seen in Breast, Prostate, Lung, Renal and Thyroid cancers.

In Breast and Prostate cancer in particular, the incidence of MBD is approximately 70% in advanced disease.

Presentation

The most common presenting feature is pain, usually exacerbated by weight-bearing and often worse at night.

Pathologic fracture occurs in about 20% of patients with MBD.

Patients may also present with symptoms of hypercalcaemia in about 20% of cases. Symptoms include generalised bone pain, nausea and vomiting, polyuria, abnormal heart rhythms, depression, cognitive dysfunction, and in extreme cases depressed consciousness.

Acute spinal cord or neural compression manifests in around 10% of patients, and bone marrow failure presenting as a pancytopaenia has been reported in up to 9% of patients with MBD.

Assessment 

Never assume that a solitary lesion is a metastasis!

A full medical history and examination must be performed and the general condition of the patient assessed.

Baseline blood tests, including a bone profile to look for hypercalcaemia, plasma electrophoresis to screen for myeloma, and tumour markers as indicated by the history and physical.

If the primary source of MBD is unknown, further investigations should be directed to finding it (CT chest/abdo/pelvis, mammogram, etc)

As a minimum, a full length radiograph of the affected bone must be obtained to rule out other lesions within the same bone. An isotope bone scan can help elicit other  sites of MBD, although it is often cold in myeloma.

If diagnostic doubt remains,  or the lesion is solitary, a biopsy is indicated. If done early, it can also help guide other investigations. Read more about the principles of how to biopsy a musculoskeletal tumour.

Assessing Fracture Risk

Mechanical or functional pain is a good indicator of imminent fracture risk, as are avulsion of the lesser trochanter, and >50% erosion through the cortex of a long bone on any view.

Mirels developed a scoring system to help rationalise the decision making process regarding the risk of pathological fracture and when to intervene with prophylactic fixation. The system has four categories scored 1-3, giving a maximum total of 12 points. Patients with scores of 8 and above are at high risk of fracture and should be considered for prophylactic fixation. The categories are:

  • Site: upper limb (1pt), lower limb (2pts), intertrochanteric (3pts).
  • Pain: mild (1pt), moderate (2pts), limits function (3pts).
  • Lesion: blastic (1pt), mixed (2pts), lytic (3pts).
  • Size: (maximal cortical destruction in any view) <1/3 (1pt), 1/3-2/3 (2pts), >2/3 (3pts).

Prognosis, pre-morbid functional status, and the likelihood that the lesion may respond to non-surgical treatment should also be taken into consideration.

Non-Surgical Treatment

Radiotherapy is usually palliative and is generally given in a single fraction. It may prevent a fracture from occurring  if the lesion subsequently heals.

Chemotherapy clearly has a role in chemo-sensitive tumours and should be discussed with oncologists in the setting of the MDT.

Bisphosphonates are a class of drug which block the mechanisms of bone resorption by stimulating apoptosis (programmed cell death) in osteoclasts, the cells which normally resorb bone. Their use is essential in cases of hypercalcaemia related to MBD. Critically, The addition of zoledronic acid to adjuvant endocrine therapy has been shown by Gnant et al to improve disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. You can read the paper by Gnant et al in the New England Journal of Medicine.

Prophylactic Fixation

Read more about the principles for surgical treatment of metastatic bone disease.

References

British Orthopaedic Association Guidance on Metastatic Bone Disease.

Mirels H. Metastatic Disease in long bones. A proposed Scoring System for diagnosing impending pathologic fracture. Clin Orthop Rel Res 1989: 249; 256-264

Limb reconstruction in children

Limb reconstruction in children after the resection of bone tumours is associated with the following particular issues:

  • Growth – predicted final leg length discrepancies of more than 3cm are most often addressed using an extendible implant, eg the Stanmore Juvenile Tumour System. The paper by Cool et al suggests how to calculate the expected growth if bone age is known.
  • Longevity of reconstruction – endoprosthetic reconstructions in children are inevitably associated with the need for revision – biological reconstructions may be preferred
  • Adaptation – children may be more able to adapt to loss of function than adults
  • Amputation – amputation in a child can lead to disproportionate limb length discrepancy at skeletal maturity, and trans-osseous amputations can overgrow and require revision. For this reason, amputations through joints may be preferred.
  • Radiotherapy – adjuvant radiotherapy can affect growth plates
  • Acetabular deformity – hemiarthroplasty of the hip is associated with subluxation as growth occurs, particularly for children under 11 years of age (1). A Collona arthroplasty of the acetabulum in which the acetabulum is reamed to deepen the socket may help. Otherwise a shelf osteotomy may be needed in later life.

(1)  van Kampen M, Grimer RJ, Carter SR, Tillman RM, Abudu A. Replacement of the hip in children with a tumor in the proximal part of the femur. J Bone Joint Surg Am. 2008 Apr;90(4):785-95.

Primary lymphoma of bone in adults

Primary lymphoma of bone (PLB) is defined as malignant, lymphoid infiltrate within bone, without evidence of lymph nodes or other tissues at presentation. It arises from the medullary cavity and manifests as a localised, solitary lesion.

It is rare, accounting for only 3% of primary bone malignancies and 5% of extra nodal lymphomas(1). Bone lymphoma is not uncommon in advanced lymphoma originating from other sites, but PLB accounts for less than 2% of all lymphomas in adults (2).

To be defined as primary bone lymphoma there must be:

(i) a primary focus in a single bone

(ii) positive histological diagnosis

(iii) no evidence of distant soft tissue or distant lymph node involvement.

However this definition of PLB is controversial. Some studies have included patients with Ann Arbor stage 1 and 2 only, whereas others have also included patients with stage 4 disease (3).  Regional lymph node involvement at diagnosis is therefore accepted by some, as is involvement of multiple skeletal sites, as long as the other criteria are met (4).

The majority of PLB is Non-Hodgkin lymphoma, with large B-cell lymphoma being the most common subtype. Other types include follicular lymphoma and Burkitt lymphoma. Differential diagnosis includes Ewing’s sarcoma, neuroblastoma, and other round cell tumours. It can also be associated with AIDS, immunosuppression and Paget’s disease.

The most common presentations are bone pain not relieved by rest, a palpable mass, pathological fracture or cord compression. About 10% have systemic symptoms at presentation including night sweats, weight loss and fever. Common sites include the femur, humerus, tibia, spine, pelvis, sternum, ribs and skull.

PLB most often involves the diametaphysis of major long bones. Radiological findings are of an aggressive pattern of lytic bone destruction and associated soft tissue mass. CT or MRI will show a large soft tissue mass and abnormal marrow attenuation without extensive cortical destruction (5).

Because PLB is rare, there have been few randomised control trials to evaluate treatment. Traditionally radiotherapy has been used as treatment with or without chemotherapy. However more recently the standard treatment has consisted of chemotherapy (CHOP regime) with or without radiotherapy depending on the histological type and stage. Several studies have established that a combination of chemotherapy and radiotherapy is better than radiotherapy alone (6,7).

The evidence is conflicting as to which regimen produces the best survival rates. Most studies are of small sample size and are therefore limited in their value in identifying prognostic factors.

A study by Alencar et al recorded progression free survival at 83% at 4 years with no difference between treatment with chemotherapy and a combination of chemotherapy and radiotherapy (8).  Jawed et al, in a review of 1500 adults, estimated 5 year survival at 58% and 10 year survival at 45%, and the only positive prognostic indicators identified were localised disease and younger age (9).

Disease free and overall survival rates have also been reported to be 78% and 91% at 5 years and 73% and 87% at 10 years, respectively (10).

Surgical management is limited to biopsy, stabilisation of pathological fracture and decompression of spinal canal compromise. There is no clear role for debulking surgery or resection.

The introduction of rituximab in March 2001 for treatment of diffuse large cell lymphoma has shown increased survival rates compared to those treated without rituximab, for example 3 year progression free survival has been demonstrated at 88% verses 52% without rituximab (11).

Dr Ruth Blackwell MBBS

GPST1

Newcastle Upon Tyne

References:

1. Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
2 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.
3 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
4 Singh T, Satheesh CT, Lakshmaiah KC, Suresh TM, Babu GK, Lokanatha D, Jacob LA, Halkud R. Primary bone lymphoma: A report of two cases and review of the literature. J Can Res Ther 2010;6:296-8
5 Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone AJR Am J Roentgenol 1999;173:1691-7.
6 Dubey P, Ha CS, Besa PC et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997;37:1087-1093.
7 Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
8 Alencar et al Primary bone lymphoma – the university of Miami experience. Leuk lymphoma. Jan 2010;51(1):39-49
9 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
10 Fidias P, Spiro I, Sobczak ML, Nielsen GP, Ruffolo EF, Mankin H, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys 1999;45:1213-8.
11 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.

Osteosarcoma

An osteosarcoma is a malignant tumour containing cells of mesenchymal origin and which is characterised by the formation of malignant osteoid.  Osteosarcomas are the most common primary bone sarcoma, but osteosarcomas also (rarely) occur in bone – in other words the prefix “osteo-” relates to the production of osteoid matrix rather than an origin in bone.

  • Incidence is around 1-2 per million per annum, which is around 131 new cases in England per annum
  • Osteosarcomas have a peak incidence in the second decade of life, and a smaller peak in the elderly
  • They classically occur in the metaphyseal regions of long bones  where most growth occurs (ie distal femur, proximal tibia, proximal humerus)
The WHO histological classification of osteosarcoma recognises the following groups:
1. Central (Medullary) tumours
  • conventional central osteosarcomas (the most common type)
  • telangiectatic osteosarcoma
  • intraosseous well-differentiated (low-grade) osteosarcomas
  • small-cell osteosarcomas
2. Surface (peripheral) tumours
  • parosteal (juxtacortical) well-differentiated (low-grade) osteosarcomas
  • periosteal osteosarcoma: low to intermediate-grade osteosarcoma
  • high-grade surface osteosarcoma

References:

Bone Sarcomas: incidence and survival rates in England – NCIN Data Briefing. National Cancer Intelligence Network 2010.

Incidence and epidemiology of soft tissue sarcoma

Soft tissue sarcomas occur with an incidence of 30 per million and represent less than 1% of all malignancies. They can occur in almost any anatomic site, but tend to occur with a frequency that reflects the volume of mesechymal-derived tissue in that region.  For example, around 55% occur in the limbs. The type of tumour varies with age: rhabdomyosarcoma is a disease of early life, whereas leiomyosarcoma is more common in the elderly.

Environmental factors associated with sarcoma include:

  • Radiation (eg after therapeutic radiotherapy)
  • Immunodeficiency
  • Occupational (eg exposure to dioxins)

Genetic factors include

  • Li-Fraumeni syndrome (inherited p53 deficiency)
  • Neurofibromatosis.

Complications of endoprosthetic reconstruction

The major complications particular to endoprosthetic reconstruction of the limb following tumour resection include:

  • infection
  • aseptic loosening
  • dislocation
  • wear
  • implant fracture
These are in addition to other complications associated with major tumour resection, regardless of the kind of reconstruction, which include:
  • wound complications
  • thromboembolism
  • neurological injury
  • vascular injury
Local recurrence of tumour might be considered a failure of local therapy, rather than a complication.