Provincial Health Services Authority (PHSA) improves the health of British Columbians by seeking province-wide solutions to specialized health care needs in collaboration with BC health authorities and other partners.
1789 cases were diagnosed with Sarcoma between 1 January 1987 and 31 December 1996. Incidence by gender and diagnosis year for the last 5 years of this ten-year interval is presented in the table.
About 37.9% of all Sarcoma incidence is due to Soft tissue sarcoma (678 cases during the ten years), 14.2% is due to Sarcoma of Bone (254 cases), remaining 47.9% are found in other tissues.
18 infants under 1 year of age were diagnosed in BC during this ten years, the oldest diagnosed person was 100 years old. Three quarters of diagnosed patients were 35 year old and older, median age at diagnosis was 57 years and the mean was 52.4. Age distribution is presented on the histogram below:
The plot indicates that the majority of patients diagnosed with Sarcoma died from causes other than Sarcoma (285 cases of death from Sarcoma), mostly from other cancers (373 cases); few died from non-cancer causes (70 cases). Median overall survival for these patients is 4.93 years, 95% confidence interval is from 4.4 to 5.94 years.
Estimated Probability of Surviving up to 1, 3, 5 and 7 Years after Diagnosis with Sarcoma
Years After Diagnosis
Overall Survival (all causes)
Bone cancers account for 0.5% of all malignant neoplasms in the human. There are three main types of bone cancer. Osteosarcoma, which arises most often in the growing ends of long bones; chondrosarcoma, which develops in the metaphysis; and Ewing’s sarcoma, which according to recent evidence may arise from primitive nervous tissue in the bones of the axial skeleton. Several additional types of bone cancer are much less common, and include chordoma, fibrous histiocytoma, and fibrosarcoma.
Osteosarcoma has a bi-modal distribution with peaks in adolescence and late in life. Early studies of incidence and mortality indicate that higher and sustained increased prevalence in young males might be related to the adolescent growth spurt. The adolescent peak for osteosarcoma appears to be related to the pubertal growth spurt, and the rising incidence after middle age has been linked to Paget’s disease.
A role for genetic susceptibility is suggested from the association of osteosarcoma with retinoblastoma and the Li-Fraumeni syndrome; and from the near-absence of Ewing’s sarcoma in Blacks and Asians. Further research is needed in this area.
No primary prevention measures are presently available. Bone cancer is rare in B.C., and no screening maneuvers have been identified to date to reduce mortality from the disease.
Miller RW, Boice JD Jr., Curtis RE, Bone cancer. In Schottenfeld D, Fraumeni JF Jr.. (Eds) Cancer Epidemiology and Prevention 2nd Ed. 1996. Oxford University Press, Oxford. Pp971-983.
Cancers of soft tissue account for about 1% of all malignant neoplasms and for about 1% of all cancer deaths. Generally speaking, the statistics in Canada indicate an upward trend in both incidence and mortality of soft tissue sarcomas.
Ionizing radiation at high doses is known to produce a variety of sarcomas, but accounts for only a small fraction of the cases. Thorotrast, vinyl chloride, inorganic arsenic, and androgenic steroids can induce hepatic angiosarcomas, and recent studies have linked soft tissue sarcomas with occupational exposures to herbicides, mainly phenoxyacetic acids and chlorophenols.
An excess of soft tissue sarcomas has been reported in patients receiving therapeutic immunosuppression for renal transplantation and other conditions, although risk is not as high as for non-Hodgkin’s lymphoma.
No recommendations regarding primary prevention can be made at this time. No screening maneuvers are available for soft tissue sarcomas.
Zahm SH, Tucker MA, Fraumeni JF Jr.. Soft tissue sarcomas. In: Schottenfeld D, Fraumeni JF Jr. (Eds) Cancer Epidemiology and Prevention 2nd Ed. 1996. Oxford University Press, Oxford, Pp984-999.
No specific screening procedures recommended for the general population.
The diagnosis of musculoskeletal and soft tissue neoplasms involves a multidisciplinary approach between clinicians, radiologists and anatomical pathologists. Histologic examination remains the gold standard in the diagnosis of mesenchymal tumors. However, the adjuvant diagnostic techniques of electron microscopy, immunohistochemistry and more recently genetic evaluation of neoplasms via conventional cytogenetics or a variety of molecular genetic techniques are increasingly used in the diagnostic workup of patients’ tumors. Appropriate clinical information must be made available to all members of the diagnostic team since it forms an invaluable component of the diagnostic algorithm used in the work up of patients.
The World Health Organization’s International Histological Classification of Tumours is used to classify neoplasms of bone and soft tissue (Reference). Two points need to be emphasized regarding these neoplasms.
1. Neoplasms of mesenchymal tissues are classified based on the microscopic resemblance of the neoplastic cells to known mature or immature mesenchymal cells. It is not based on the tissue site of origin of the neoplasm. For example, sarcomas that demonstrate skeletal muscle differentiation are classified as rhabdomyosarcomas because the individual neoplastic cells demonstrate cytoplasmic evidence of skeletal muscle differentiation. In fact, rhabdomyosarcomas rarely arise in the large skeletal muscles and commonly develop in regions which normally contain no or scant numbers of mature skeletal muscle cells (the lower genital tract).
This raises the question as to what is the "cell of origin" of the various neoplasms that constitute the mesenchymal tumors. In the vast majority of cases the answer to this is unknown. Current theories suggest that there are ubiquitously distributed mesenchymal cells throughout the skeleton and somatic soft tissues that have the capacity to differentiate into a variety of different mesenchymal cell types. These "pluripotential" cells likely represent the population that result in the majority of mesenchymal neoplasms. Most of the time the circumstances or signals that result in the development of the neoplastic phenotype are unknown. A proportion of mesenchymal neoplasms are composed of cells that do not resemble any known immature or mature mesenchymal cells. These latter neoplasms are typically designated in a descriptive manner (e.g. alveolar soft part sarcoma).
2. Unlike epithelial neoplasms in which there is a clearly recognized and biologically understood pathway that explains the development of malignant neoplasms on the background of pre-existing benign neoplasms (the adenoma-carcinoma sequence), the development of a sarcoma in the setting of a pre-existing benign mesenchymal neoplasm is rare. There are a number of uncommon hereditary syndromes in which benign mesenchymal neoplasms have a recognizable risk of "malignant degeneration", (Neurofibromatosis type I, multiple hereditary osteochondromatoses, multiple enchondromatosis). However numerically the sarcomas arising in these conditions constitute a tiny fraction of all sarcomas. The more usual circumstance in sarcoma is for the malignancy to develop de novo. On occasion, low grade, slow growing sarcomas may transform into high grade, biologically aggressive sarcomas. This phenomenon is known as "dedifferentiation" and most characteristically arises in low grade osseous chondrosarcomas and low grade soft tissue liposarcomas. Under these circumstances the behavior of the neoplasm, and by extension, the management of the patient, will be significantly altered by the presence of the high grade component of the neoplasm.
The reporting of soft tissue sarcoma biopsy and/or resection specimens should include in addition to all of the patients demographic information the following points
Though morphological characteristics recognized in histopathologic grading of tumours generally correlate with biological behavior, a more complete assessment of the tumor and its spread(i.e., staging) is necessary for planning treatment and comparing results. No single clinical staging system for musculoskeletal tumours and sarcomas has been accepted.
At the present time two systems of staging are being used:
Efforts are currently being made to consolidate these two systems into a more meaningful staging system.
The Staging sheet includes a statement of the site of the primary, the final diagnosis and the staging using the Enneking staging system. It must be signed and dated by the attending physician.
It is incumbent upon the primary care physician:
A high index of suspicion of malignancy is essential, for example, in a teenager with knee pain unrelated to trauma or persisting longer than it should or in the patient over fifty years old with the same clinical presentation in whom metastatic disease to bone becomes increasingly common.
Similarly, when the complaint is a deeply located large soft tissue mass, soft tissue sarcoma must be considered in the differential diagnosis so that appropriate baseline investigations may be done.
The Musculoskeletal Tumor and Sarcoma Group have become increasingly aware of frequently encountered pitfalls in early management. These make the definitive treatment of these lesions more difficult, more complicated and less satisfactory. It has been our experience that nearly one in three patients have not received ideal oncologic management due to errors in investigation, diagnosis or treatment.
The major problem encountered is related to the biopsy which is discussed here prior to other considerations, ONLY to emphasize that it should NEVER be done before other appropriate staging procedures. Caution should be exercised in carrying out invasive procedures. Above all, a BIOPSY must not precede other investigations for fear of interfering with their results.
The goal of biopsy is to harvest a representative sample of the tumor without compromise of the definitive management. Sarcomas are tumors that are known to be able to spread by implantation. It should be done only when
Investigations may include:
1. PLAIN RADIOGRAPHSA plain X-ray is the most important initial investigation of a potential bone neoplasm. It is helpful in the investigation of soft tissue lesions particularly if the lesion is mineralized.
2. MAGNETIC RESONANCE SCAN (MR SCAN)The MR scans have become vital in the management of musculoskeletal tumours and sarcomas because they:a) provide detailed information that has increased our ability to safely excise lesions that formerly were felt to be inoperable.b) are particularly helpful in evaluating the extent of soft tissue lesions and their relationships to surrounding vital structuresc) aid in the evaluation of the medullary canal of long bones valuable in the search for such things as skip metastases in osteosarcomas.d) on occasion may lead to a diagnosis based only on the MR signal characteristics of the lesion, as is the case in intramuscular lipomas or low-grade liposarcomas (lipoma-like).
The MR scan is severely affected by the BIOPSY PROCEDURE and should be done BEFORE THE BIOPSY is performed. The scan is very sensitive to reactive edema and post-procedural scans can be difficult to interpret.
3. COMPUTERIZED TOMOGRAPHY (CT SCAN)This examination has become an essential part of the staging studies necessary for planning treatment, particularly FOR:a) STAGING the lungs (The chest CT scan is very sensitive and false positives are common and over interpretation is to be avoided. Plain chest radiographs are usually recommended for chest follow up.)b) GUIDING core needle biopsies FOR most cases.
4. RADIONUCLEOTIDE SCAN ("BONE SCAN")A total body technetium scan will give useful information:a) not only about a presenting bone lesionb) but also about possible multiple lesions and bone reaction to overlying sarcomas.
A bone scan is generally not indicated in soft tissue tumors.
5. TOMOGRAPHY - NO LONGER ROUTINELY USED.
6. ANGIOGRAPHYa) has a limited place in investigation of musculoskeletal tumours and sarcomasb) is useful in the investigation and treatment of hemangioma, arterio-venous malformation, and metastatic renal and thyroid carcinoma.
7. ULTRASOUND EXAMINATIONSUltrasound has no routine application in the pre-biopsy evaluation of solid soft tissue lesions occurring at any site. They maybe misleading, particularly when the radiologist attempts to make a diagnosis. The ultrasound scan simply serves to delay the diagnostic process, and should not be ordered. The single most important test for a bone or soft tissue sarcoma is the magnetic resonance scan (MR scan).
In general, the Sarcoma Group supports the following principles of referral:
Primary referral – untreated patients
Referral to the Agency after the diagnosis of musculoskeletal tumor or sarcoma, either recent or remote, should be accompanied by all available information on the patient at the time of referral. This information might include clinical and laboratory information, investigations and X-rays, surgical observations and pathologic material. Because of short intervals to new patient appointments –imaging is best carried to the appointment by the patient so it is available for the consulting doctor at the time of the appointment.
Any patient less than seventeen years of age at PRESENTATION should be referred to the Paediatric Oncology Division of the Cancer Agency located at the BC Children's Hospital(BCCH) or the Paediatric orthopedic surgeon at the BCCH (Dr. Ken L. B. Brown, (604) 875-2642 ). The principles of treatment (particularly in regard to biopsy and surgical treatment) remain the same but there are certain unique characteristics of these tumours recognized in this age group.
All patients should be referred to a tertiary cancer center either BC Cancer Agency or the BC Children's Hospital. Below are the numbers to contact if you are referring a new patient:
BC Cancer Agency
Vancouver Cancer Clinic
Fraser Valley Cancer Clinic
Cancer Clinic of the Southern Interior
Vancouver Island Cancer Clinic
(250)370-8228, Local 2439
BC Children's Hospital
The guiding principle of surgical intervention is complete removal of the primary tumor with maximum retention of function and minimum possibility of local recurrence. Classically, in extremity tumours, this has been accomplished by ablative surgery (amputation). Today, the increasing use of limb salvage procedures has become possible because of effective adjuvant radiation therapy(see below). Neo- adjuvant chemotherapy may contribute in some instances by reducing tumor edema and size and by eradicating micrometastases. As a result, it becomes even more essential that a multi-disciplinary treatment team plan the overall management recommendations from the beginning.
curettage, debulking or piecemeal removal
This procedure may be appropriate for some benign tumors, but never for malignant tumors
This procedure transgresses the pseudo-capsule (zone of reaction), microscopic tumor is left behind and opened tissue planes are contaminated.
Local recurrence is 100% in high-grade lesions and high in lower grade entities.
wide local excision
The neoplasm is removed outside its reactive zone, with an adequate but variable amount of "normal" tissue attached to it. In soft tissue sarcomas, unless the margin is extremely wide, there remains a likelihood of local recurrence.
The tumor and surrounding tissues are removed by dissecting along planes that are separated from the tumor and its tissue of origin by at least one involved anatomical structure in both longitudinal and transverse planes.
*The procedure amputation may fit into any one of these four categories as inadequate (or adequate) surgical treatment.
** For musculoskeletal lesions
Unresectable metastatic disease is not curable for the majority of patients a primary diagnosis of sarcoma. Most sarcoma patients require resection of the metastases to improve their chance of cure. Post resection, chemotherapy may not add to the curability of a patient with soft tissue sarcoma though some patients with metastatic Ewings sarcoma or rhabdomyosarcoma maybe cured by chemotherapy without operative intervention.
A patient will be considered for resection of skeletal or pulmonary metastasis if:
Surgery is also considered to palliate pain or prevent fracture or debility when appropriate.
Revised 4 January 2012
A recently published nomogram (Gold, Lancet Oncology 2009) assesses risk of recurrence based on those factors. The sarcoma systemic team are assigning risk categories using that nomogram as follows:
Very low risk
Discharge – no recommended routine follow-up testing
We recommend clinical evaluation, CBC, LFT’s, creatinine and CT scan at 6 months interval X 1yr; then yearly X 4 years.
These patients can be
discharged if adequate follow-up care available in the community.
Adjuvant Imatinib 400 mg PO Daily (SAAJGI) X 3 yrs for all high risk patients (Joensuu J Clin Oncol 29: 2011 (suppl; abstr LBA1). Protocol code SAAJGI. No CAP required. Class 2 drug application required outside BCCA.
Adjuvant Imatinib -The ACOSOG study Z9001showed that adjuvant Imatinib (400 mg dose daily for 1 year) was beneficial, especially for subjects with tumours 10cm or greater who have a relapse rate of 50% at 1 year and 75% by 2 years vs 5% and 25% for the Imatinib treated groups. As yet overall survival improvement has not yet been seen. At ASCO 2011, Joensuu reported on the Finnish group’s randomized adjuvant study for high risk patients with resected GIST comparing taking standard dose Imatinib for 1-year versus 3-years. At a median follow-up of 4.5 years, there was significant relapse-free and overall survival benefit for the 3-year arm (Joensuu, J Clin Oncol 29: 2011 (suppl; abstr LBA1)).
Radiation is used for both curative treatment and for palliation. It may be used alone or in conjunction with surgery and/or chemotherapy. The radiation oncologist is an integral part of the sarcoma management team that performs a preoperative assessment of patients with possible sarcomas.
Combined with surgery, radiation therapy has
It is essential that there is good communication between the surgeon and radiation oncologist to ensure that these two modalities are combined to their best effect.
Pre-operative Radiation Therapy
Post-operative Radiation Therapy
* Larger radiation treatment volume required. If there is wide surgical disruption of tissues radiotherapy treatment will be severely compromised.
Primary, curative radiotherapy may be used alone to ablate local disease:
Adjuvant radiotherapy combined with wide or radical excision is the best means of achieving local control of disease or most patients. The radiotherapy course is fairly standardized. Doses can be modified depending on the treatment volume and the proximity and nature of surrounding normal structures. Planning may involve computerized tomography and specially made devices for immobilization. A radiotherapy treatment course will usually take 4 to 6.5 weeks and treatment will be given once daily on weekdays.
Early side effects include skin erythema and desquamation (especially in skin creases). Late side effects include fibrosis of subcutaneous tissue and skin atrophy. It is essential that one third of the circumference of a limb be kept out of the radiation field if at all possible. If not, circumferential scarring can occur resulting in an increased risk of subsequent lymphedema and loss of the vascular supply to the limb. Hence the importance of well placed scars.
Radiotherapy can be used to palliate symptoms from incurable sarcoma. It is usually possible to use standard short palliative courses. Sometimes higher doses are required to achieve local control.
Revised 17 May 2010
Chemotherapy may be combined with surgery or radiation therapy in the curative management of some patients with sarcoma.
Chemotherapy can be helpful for palliation in selected patients with metastatic disease who have
Standard drug therapy is single agent Adriamycin (SAAVA) which despite a response rate of 25 - 30 % affords equivalent prolongation of survival as compared to more modern single agent protocols or combinations. There is no curative drug therapy for metastatic inoperable soft tissue sarcomas. In some patients with peripheral neuroectodermal tumours and rhabdomyosarcoma, cure can be achieved with chemotherapy. Occasionally high does chemotherapy with stem cell support may be offered in those instances.
New drug development remains a very high priority for oncologists treating metastatic sarcomas. BCCA oncologists participate in studies testing new chemotherapy drugs combinations and/or new drugs for the treatment of patients. Some of these new drugs are modifications of older drugs known to have some activity; others are new types of drugs, such as signal transduction inhibitors. The latter are very attractive for patients who have types of tumors with readily identifiable genetic markers, e.g. c-kit in GIST. Unfortunately not every patent is eligible for every study but available studies will be discussed with the individual eligible patient.
1) Ewing's Sarcoma and Other Small Round Blue Cell Tumors:
2) Osteosarcoma /Malignant Fibrous Histiocytoma of Bone (MFH of Bone) / other High Grade or Spindle Cell Sarcomas of Bone
Adjuvant chemotherapy has now been established as an essential part of the management of osteogenic sarcoma. Randomized studies show a significantly improved overall survival for non-metastatic osteosarcoma patients treated with adjuvant chemotherapy (Link, Eilber). Spindle cell tumors of bone are also believed to benefit from adjuvant chemotherapy and are generally managed in the same osteosarcoma.
Once the staging studies have been completed and a biopsy diagnosis made, preoperative administration of a multi-drug program is preferred.
Lack of tumor necrosis seen in the final operative specimen in some instances may result in a change in the recommended post-operative regimen.
Patients with operable pulmonary metastatic disease at diagnosis or subsequently may be cured and therefore are treated aggressively with thoracotomy with or without chemotherapy.
Rhabdomyosarcomas are tumors which occur primarily in the Pediatric age patient.
The primary management involves neoadjuvant chemotherapy, followed by surgery and radiation therapy.
In the adult setting, the protocols used are derived from the Paediatric group recommendations.
Adult patients are often treated in a manner similar to Ewings/PNET patients.
4) Adjuvant Chemotherapy for Other Soft Tissue Sarcomas
The role for routine adjuvant chemotherapy for soft tissue sarcoma patients remains controversial, but we recommend its discussion with patients in the following situations:
Revised 15 June 2010
The broad ranging types of musculoskeletal tumours and sarcomas prohibit a rigid recommendation with respect to follow-up.
4) Summary of standard recommendations below.
Follow-up is generally indicated where early detection of an abnormality may result in cure.
Areas of concern:
if a second wide excision is possible it may achieve a cure providing there is no sign of metastasis. Therefore intensive follow-up with examination of the primary site is recommended every 3 months and if superficial this may be sufficient. If the primary was deep the examination should be supplemented by scans (CT or MR) every 6 months.
surgery is not possible or can not achieve a cure follow to assess symptoms from treatment or disease at 6 monthly intervals. No imaging tests are indicated unless symptoms arise.
In those with
osteosarcoma, wedge excisions of the metastases can achieve long term survival. Quasi adjuvant chemotherapy may also be recommended. CXR of the lungs every 3 months for 2 years then every 6 months till 5 yrs of follow-up completed – then yearly.
For patients with
soft tissue sarcomas, the role of metastasectomy is controversial as there has not been routine benefit noted at meta-analysis. Patients who would be fit enough to undergo thoracotomy and felt to be going to benefit from resection of metastases if detected are generally followed with routine CXR as above.
For example, complications from combined resection and radiotherapy of a limb, radiotherapy to abdominal organs compromising function of the bowel or kidneys.
Rigorous follow-up is less important for this small minority of patients. They should be followed as for other patients with incurable disease.
Adult Soft Tissue Sarcomas
Bone tumours, Ewing’s and Rhabdomyosaroma
Special situations (see below)
Yr 1- 2 Every 4 months
Yr 3,4,5 Every 8 months
Yearly to continue
Yr 1- 2 Every 3 months
Yr 3,4,5 Every 6 months
Yearly to continue
& X-rays operative site if bone primary
Yr 1,2 Every 4 months
CXR Yearly to 10 years
Yr 1,2 Every 3 months
CXR Yearly to 10 years
If suspicious lesion(s) encountered, chest CT scan is indicated if surgery for cure is an option.
CT or MR
Baseline 3 – 6 months after treatment
Baseline 3 – 6 months after treatment
For patients with deeper, proximal or axial tumours:
To be done at completion of treatment and again only at recurrence
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