Spindle Cell Sarcoma of the Bone

Spindle cell sarcoma is a soft-tissue tumour which can start in the bone. Spindle cell sarcomas of the bone are often found in the arms, legs and pelvis. They most commonly arise in patients over the age of 40 and are extremely rare, making up just 2-5% of all primary bone cancer cases.

Spindle cell sarcoma is referred to in this way due to the appearance of its tumour cells when they are looked at under a microscope. The cells which make up a spindle cell sarcoma are long and narrow, which is known as a ‘spindle-cell shape’(1).

There are three subtypes of spindle cell sarcoma of the bone:

• Pleomorphic Undifferentiated Sarcoma (previously known as Malignant Fibrous Histiocytoma)
• Fibrosarcoma
• Leiomyosarcoma

The majority of spindle cell sarcomas follow the same diagnosis and treatment methods as osteosarcoma, a more common type of primary bone cancer. (1,3)

Spindle cell sarcoma can arise in any bone, in any area of the body, though the majority of these tumours are found in the long bones of the body. These include the thigh bone (known as the femur), the area around the knee, the shin bone (known as the tibia) or the upper arm (known as the humerus)(1,2). Additionally, one type of spindle cell sarcoma, known as undifferentiated sarcoma of the bone, is quite commonly found in the pelvis and fibrosarcomas can develop in the head and neck area.

The different types of spindle cell sarcoma of the bone can overlap with one another in their appearance. There is still some variation in the terminology used amongst health care professionals surrounding the diagnosis of this tumour. For this reason, the exact number of spindle cell sarcoma of the bone cases is still largely unknown, though it is reported that they make up just 2-5% of all primary bone cancer cases. There is a slightly higher number of cases seen in male patients than in female patients(1).

This type of cancer can affect anyone, at any age. Though spindle cell sarcoma is most commonly diagnosed in adulthood, affecting patients over the age of 40 years old(3).

There are three different types of spindle cell sarcoma of the bone and these are able to start in any bone in the body. For this reason, the symptoms experienced by patients can vary between patients and it is difficult to predict the exact symptoms an individual may face.

Often, the symptoms are common and difficult to pinpoint to one disease. Hence, early diagnosis is not always possible and in some cases the tumour may be relatively advanced before the symptoms are reported or confirmed as a spindle cell sarcoma of the bone.

The most commonly reported symptoms of spindle cell sarcoma patients are:

• Bone pain – this may be continuous or may come and go
• A pathological fracture may occur*– this is a fracture that has occurred due to the weakening of a bone from a disease
• Swelling
• The presence of a lump or mass
• Tenderness in the area
• Reduced mobility of the area, or of a joint in a nearby location to the affected area
• Fatigue – which is extreme tiredness caused by a disease
• Malaise – which is the general feeling of unwell and discomfort

*A pathological fracture of the bone can encourage the circulation of tumour cells which leads to the local spread of a spindle cell sarcoma. Therefore, it is important that if a pathological fracture presents it is investigated further.

For more information on the symptoms of primary bone cancer please refer to our About Primary Bone Cancer information section.

There are three types of spindle cell sarcoma of the bone(1,3). These three types can be classified by radiologists (who look at images of the tumour following diagnostic scans) or by pathologists (who look at the type of cells in the tumour under a microscope following a biopsy of the bone).

The three types of spindle cell sarcoma are:

• Pleomorphic Undifferentiated Sarcoma (also known as Malignant Fibrous Histiocytoma)
• Fibrosarcoma
• Leiomyosarcoma

Pleomorphic Undifferentiated Sarcoma (also known as Malignant Fibrous Histiocytoma)

Pleomorphic undifferentiated sarcomas were previously known as malignant fibrous histiocytomas (referred to as MFH)(4). The change in the naming of this tumour type is due to an increased knowledge of spindle cell sarcoma, which has allowed other tumours of the connective tissue (such as leiomyosarcoma and rhabdomyosarcoma), to be accurately diagnosed as separate tumours to MFH. Therefore, the tumours that would still be classified as an MFH are now known as their own tumour type, called a pleomorphic undifferentiated sarcomas.

Unlike the other types of spindle cell sarcomas, pleomorphic undifferentiated sarcoma of the bone are not made up of any particular specialised cell. Instead, the cancerous cells of the bone are relatively undeveloped and it is difficult to determine which normal cell type they have developed from.

Undifferentiated pleomorphic sarcomas tend to occur in older patients, aged around 60 to 70 years of age(4).

Fibrosarcoma

Fibrosarcomas are very rare and are mostly found in middle-aged adults This type of sarcoma is referred to as a fibrosarcoma as it is predominately made up of specialised cells known as fibroblasts. Fibroblasts create the structural framework of many tissues(5).

The most common location for a fibrosarcoma to occur is the thigh bone (which is known as the femur).

Leiomyosarcoma

Leiomyosarcoma of the bone is extremely rare and therefore there is little known about this spindle cell sarcoma subtype. It is characterised by the presence of cells known as ‘differentiated smooth muscle cells’, but tends to be managed in a similar manner to osteosarcoma - a more common form of primary bone cancer(6).

Although leiomyosarcoma can affect a wide range of patients, it is known to affect middle-aged patients most often(2,6).

Spindle cells make up part of the body’s natural healing process in response to injury. Normally, once the area being repaired has healed, spindle cells will stop dividing to prevent the build-up of these cells. However, spindle cell sarcoma forms when these spindle cells begin to divide uncontrollably, creating a mass of cells that forms a tumour.

Some individuals may have a genetic predisposition to spindle cell sarcoma. This means gene irregularities are passed down from their family members, making them more likely to develop this cancer. In addition to this, there are numerous conditions, or diseases, of the bone that are linked to the development of a spindle cell sarcoma.

Some causes and risk factors that increase the likelihood of an individual developing a spindle cell sarcoma include:

• Paget’s Disease of the Bone

Paget’s disease of the bone is a condition that causes the bones to become weakened and misshapen. This can increase the risk of a patients developing diseases of the bone, such as spindle cell sarcoma(1,2,7). For more information of Paget’s disease please visit The Paget’s Association.

• Undergoing previous radiotherapy

For previous radiotherapy to be classified as a risk factor of spindle cell sarcoma, the affected bone must have been included in the field of radiation. There is usually a long period, usually 9 years or more, that pass before the sarcoma will develop following radiotherapy(1)

• Fibrous Dysplasia

Fibrous dysplasia is a common disorder of the bone which replaces normal bone tissue with undeveloped connective tissue. On very rare occasions, this has been known to lead to the development of fibrosarcoma (a subtype of spindle cell sarcoma)(5,7)

• Bone Infarction

Bone infarction is the death of bone tissue in areas due to a poor blood supply and therefore a lack of oxygen to bone(5)

• Osteomyelitis

Osteomyelitis is the inflammation of the bone or the bone marrow(5,7)

Patients with different types of primary bone cancer are assessed in similar ways. For this reason, diagnostic tests are covered in more detail in our About Primary Bone Cancer information section.

Going to the doctor

The symptoms of spindle cell sarcoma can be non-specific and may be different depending on the exact location of the tumour and the tumour type. It is important that an accurate diagnosis is made, confirming the type of spindle cell sarcoma that is presenting, to allow the most appropriate treatment plan to be put into place.

People report a variety of experiences when they seek medical advice about their symptoms. Most people with worrying symptoms go to their GP.

Some patients go to their local hospital emergency department (A&E) or other health care centres.

Some people are referred quickly for further tests or a second opinion, but often patients have to return to their GP three or four times before they are referred for more tests. Primary bone cancers are very rare and many GPs will never come across a case.

If a GP or hospital doctor is concerned about the patient's symptoms, there are national guidelines they should follow. According to the National Institute for Clinical Excellence (NICE) Guidelines for Suspected Bone Cancer and Sarcoma:

• Children, teenagers and young adults with unexplained bone swelling or bone pain should have an urgent X-ray within 48 hours. If the X-ray suggests a possible bone cancer, your GP should refer you to a specialist within 48 hours.
• Adults should be seen by a specialist within 2 weeks if the results of an X-ray suggest a bone cancer.

If the X-ray is normal but symptoms persist, the patient should be followed up and/or a repeat X-ray or MRI scan should be carried out within 2 weeks (adult) or within 48 hours (child) or a referral requested to a specialist.

Bone Cancer Awareness Initiative

The Bone Cancer Research Trust is trying to find ways to make the time between the start of symptoms and getting the diagnosis much shorter. Our 2020 Patient Survey report is the most comprehensive analysis of presenting symptoms and routes to diagnosis for primary bone cancers & tumours in the UK to date. This is our evidence base on which we will focus our awareness objectives moving forward.

The report focuses on two main areas - the time and routes to diagnosis and the range of presenting symptoms across all anatomical locations and forms of primary bone cancer & bone tumours.

Our analysis found that patients wait, on average, more than 7 months and make 8 visits to the multiple healthcare professionals before receiving an accurate diagnosis.

Going to a Bone Cancer Centre for more tests

Once an abnormality is found in a bone that suggests the possibility of cancer, the patient will be referred to a bone cancer surgical centre.

Bone cancer surgical centres are specialist hospitals. They have a group of healthcare specialists who are experts in the diagnosis and management of bone cancer.

In England, there are currently five bone cancer centres which specialise in the diagnosis and management of primary bone cancers. These centres are at Birmingham, Newcastle, Oswestry, Oxford, and Stanmore.

In the Republic of Ireland, there are no specific bone cancer centres. Patients are initially seen in their local hospital and subsequently referred to specialist hospitals in Dublin or Cork for further tests and, if necessary, for treatment.

Patients in Wales usually travel to Oswestry or Birmingham for these specialist tests.

In Scotland there are five sarcoma centres and so patients travel to one of these centres for diagnosis if primary bone cancer is suspected. These centres are in Edinburgh, Glasgow, Inverness, Aberdeen and Dundee.

In Northern Ireland, patients are usually seen in Belfast.

For a full list of locations patients may be referred to in order to confirm a primary bone cancer diagnosis please click here.

The MDT

Specialists in many different areas of medicine at the bone sarcoma centres, the Regional Cancer Centres in the UK and hospitals in Ireland work together as a 'Multidisciplinary Team' (MDT). The members of the MDT work together to diagnose the patient's condition.

The MDT includes:

• Specialist bone sarcoma surgeons.
• Specialist sarcoma oncologists (oncologists are doctors who look after people with cancer).
• Specialist sarcoma pathologists (pathologists are doctors who use laboratory techniques to diagnose disease).
• Radiologists (doctors who diagnose disease and conditions from looking at x-rays, or scans).
• Sarcoma cancer nursing specialists (sometimes called 'CNS') who perform an essential role in treating and caring for primary bone cancer patients.

What tests are done?

When a person is referred to a bone cancer surgical centre, further tests will be done to find out more and to confirm whether the patient has bone cancer, and if so what type.

These tests may include:

X-ray

X-rays of the bone may be taken, including the joints above and below, and are studied. These X-rays may show swelling around the bone or areas of abnormal bone growth. A chest x-ray is sometimes taken to show whether the cancer has spread to the lungs. Cancer Research UK gives more information about X-rays.

Blood tests

These include:

• Blood chemistry (Urea and Electrolytes) is checked to examine the levels of normal salts and urea and creatinine, which are waste products. This test can give clues to how well the kidneys are working
• Full blood count (FBC) counts the numbers of different types of blood cells in the patient's blood at that time.
• Red blood cells - which carry oxygen in the blood.
• White blood cells - which are essential to the immune system (and totals of each type).
• Platelets - which are essential to the making blood clots and scabs.
• Levels of haemoglobin - which is found in red blood cells.
• Liver function tests (LFTs) to see how the liver is working.
• Erythrocyte Sedimentation Rate (ESR) is a test to look for signs of inflammation.
• C-Reactive Protein (CRP) levels are tested as CRP levels increase in inflammation.
• Alkaline phosphatase (ALP) levels are measured in patients with suspected osteosarcoma.

Cancer Research UK gives more information about blood tests.

MRI scan

Spindle cell sarcomas of the bone often present with a pathological fracture; this is a fracture of the bone that has occurred due to the bone being weakened in the presence of a disease. A pathological fracture of the bone may mean that there is an opportunity for the cancerous cells to escape from the tumour into the blood stream, causing the spread of the spindle cell sarcoma to other areas of the body. Therefore, it is important that if a pathological fracture occurs it is investigated further using an MRI scan to determine the reasoning behind this fracture(1).

MRI stands for 'magnetic resonance imaging'. This type of scan is similar to a CT scan but magnetism and radio waves are used instead of x-rays to build up a very detailed 3-dimensional image.

An MRI scan of the entire bone is used to gain more information about the tumour in the bone. An injection of a special dye, known as a contrast agent is also used. This makes certain tissues show up more clearly and with greater detail on the scan. The results of the scan will be examined by a radiologist and a report will be produced. For some patients they may also have a total body MRI scan to look for areas of abnormalities in the other bones such as tumour spread (metastases).

Cancer Research UK gives more information about MRI scans.

CT scan

CT stands for 'computerised tomography'. They may also be called CAT scans, which stands for 'computerised axial tomography'.

The scanner takes x-rays from many different angles and a computer builds up a 3-dimensional picture of the body in great detail. The pictures show cross-sections of the inside of the body.

CT scanning of the lungs shows up any secondary tumours where the cancer may have spread (metastases). It is used if the MRI scan results have not been able to confirm the diagnosis of osteosarcoma.

Cancer Research UK gives more information about CT scans.

PET scan

PET stands for 'positron emission tomography.' Not all hospitals have PET scanners but they are used to detect spread or metastases in osteosarcoma.

PET scans can examine the whole body, rather than a specific area. They can also detect how well treatments are working.

Before the scan, a small injection of radioactive glucose (a radiotracer) called fluorine18 will be given.

The tracer will take around an hour to spread around the body. During the scan, which can last about an hour, the patient lies on a bed and the scanner passes over them. The scanner detects where the radiation is concentrated and produces images. Hot spots on the PET scan can detect metastases.

The results of the scan will be examined by a radiologist.

Cancer Research UK gives more information about PET scans.

Biopsy

A bone biopsy is a specialised procedure that can be performed by a specialist in orthopaedic surgery or sarcoma radiology at a bone cancer surgical centre. A biopsy involves taking a small sample of a lump or tumour so that a pathologist can examine the cells in the sample and determine whether the lump is cancerous or not.

The biopsy being taken may be a ‘needle biopsy’ or an ‘open biopsy’.

• Needle biopsy: a needle is inserted into the tumour to draw out a small amount of tumour tissue (this may be done under local anaesthetic). Often, in order to know exactly where to take the sample from, this test is carried out alongside an X-ray or CT scan to guide the doctor.
• Open biopsy (or surgical biopsy): is used less frequently than a needle biopsy. This form of biopsy is carried out during a small, minor, operation to remove a small piece of tumour while under general anaesthetic. This test tends to be used if a needle biopsy does not provide a diagnosis and the doctor wish to investigate further.

Cancer Research UK gives more information about bone biopsies.

Spindle cell sarcomas of the bone often present with a pathological fracture; this is a fracture of the bone that has occurred due to the bone being weakened in the presence of a disease. A pathological fracture of the bone may mean that there is an opportunity for the cancerous cells to escape from the tumour into the blood stream, causing the spread of the spindle cell sarcoma to other areas of the body. Therefore, it is important that if a pathological fracture occurs it is investigated further using an MRI (magnetic resonance imaging) scan to determine the reasoning behind this fracture(1).

X-Rays, CT (computerised tomography) scans and MRI scans cannot definitively diagnose a spindle cell sarcoma of the bone. However, these scans can provide important information on the location of the tumour, the size of the tumour and determine if the tumour has spread elsewhere in the body. These scans also look if there is any damage to the bone, which can let doctors know how advanced the tumour is.

To learn more about biopsies please see our About Primary Bone Cancer information section.

An alternative diagnosis?

When diagnosing spindle cell sarcoma of the bone it is important to rule out the presence of various other diseases, or conditions, which may appear in a similar manner to a spindle cell sarcoma in terms of signs and symptoms. It is important the correct diagnosis is made to ensure the treatment provided is suitable. It can sometimes take a long time to confirm a diagnosis of primary bone cancer after a biopsy, this is because these tumours are rare and sometimes difficult to identify. Diseases with similar symptoms or signs are known as ‘differential diagnoses’.

If the diagnostic tests show that the patient does not have a spindle cell sarcoma of the bone, there are a number of other conditions that may be presenting, including:

• Osteolytic Osteosarcoma

Spindle cell sarcomas are known to behave in a similar manner to osteosarcoma, a common form of primary bone cancer, and are therefore treated in a similar manner. Clinicians are able to tell the difference between these two cancers of the bone as spindle cell sarcomas do not produce a bony substance known as osteoid, which osteosarcomas do(1,2)

• Metastatic Carcinoma

When a cancer spreads from one area of the body to form a tumour in another area of the body, the secondary tumour is known as a metastatic carcinoma. Many cancers spread to the bone, including those from the breast, lung and kidney, and so an angiosarcoma of the bone is often thought to be a metastatic carcinoma(1).

• Aneurysmal Bone Cyst

An aneurysmal bone cyst is a non-cancerous, blood-filled cyst which can start in any bone in the body. These cysts grow in the bone and cause pain and possible fracturing - which are signs and symptoms seen in spindle cell sarcoma(5,8)

Where will treatment take place?

Surgery needs to take place at one of the bone cancer surgical centres (see map below, blue stars). Chemotherapy and radiotherapy can take place at different hospitals around the UK and Republic of Ireland. The delivery of intensive chemotherapy should be administered at one of the specialised cancer centres. For patients whose nearest specialist hospital is far away, a 'shared care' arrangement for acute issues and unexpected admissions with a closer hospital might be set up. The specialist hospital can be reached for advice on acute presentations and outpatient management.

England and Wales

Diagnosis and surgery should take place in one of the five bone cancer centres (see the map below):

• North of England Bone and Soft Tissue Tumour Service - Newcastle Teaching Hospitals NHS Foundation Trust
• Oxford Sarcoma Service - Nuffield Orthopaedic Centre
• London Sarcoma Service - Royal National Orthopaedic Hospital
• Greater Manchester and Oswestry Sarcoma Service - Robert Jones & Agnes Hunt Orthoapedic Hospital, The Christie Hospital, Manchester University NHS Foundation Trust
• The Royal Orthopaedic Hospital, Bristol Road South

Scotland

Patients are treated at one of the five Sarcoma Centres that are part of the Scottish Sarcoma Network. These hospitals are in Aberdeen, Dundee, Edinburgh, Glasgow, and Inverness. Patients visit one of these five Sarcoma Centres for chemotherapy or radiotherapy treatment. For surgery, primary bone cancer patients are seen in Glasgow, Edinburgh or Aberdeen.

Republic of Ireland

Most patients aged under 16 receiving chemotherapy fare treated at Our Lady's Hospital, Crumlin, Dublin.

Patients aged 15-19 are treated at Mater Misercordiae Hospital, Our Lady's Hospital, Crumlin and Waterford Regional Hospital.

Patients aged over 20 are treated at Mater Misercordiae Hospital, Our Lady's Hospital Crumlin, Sligo General Hospital, Cork University Hospital, Waterford Regional Hospital, St Vincent's Hospital and Mercy Hospital.

For surgery, most patients in the Republic of Ireland (all ages) go to St. Marys Orthopaedic, Cappagh. For radiotherapy most patients attend St Luke's and St Anne's Hospital, Dublin. However, some patients may also attend other hospitals in Dublin and Cork.

Key

Red stars: Specialist Children's Cancer and Leukaemia Centre
Blue stars: Bone Cancer Surgical Centre
Green stars: Children and Young People's Integrated Cancer Service
Purple stars: Teenage Cancer Trust Unit
Yellow stars: Scottish Sarcoma Network Hospital

Please see our full list of centres providing treatment for primary bone cancer here.

Treatment: Overview

Phase 1 - Neoadjuvant Chemotherapy

Chemotherapy given before surgery is called neoadjuvant chemotherapy.

Following the diagnosis and the first tests, patients are given a combination of chemotherapy drugs. The number of drugs and how long for and how many times they are given can be different from country to country.

The number of chemotherapy drugs can vary from 2 to 4 and these can be given for between 6 and 12 weeks.

In the UK, Ireland, much of Europe and the USA the current standard treatment before surgery is made up of 3 chemotherapy drugs given over 10 weeks. The aim of this course of chemotherapy is to shrink the primary tumour and to kill any cancer cells that have spread to other parts of the body.

Phase 2 - Surgery

Following this first round of chemotherapy, the aim is to treat the main tumour site. Where possible, patients have surgery to remove the primary bone tumour. This is more likely to be possible if the tumour is in a limb (arm or leg) or easily accessible position in the body. For many patients the main tumour is not easily removable, for example if the tumour is in the pelvis or spine.

The decision about whether surgery is possible is usually taken by the multidisciplinary team.

The aim of surgery is to remove the primary tumour safely and at the same time try to keep the body working as normally as possible. If the primary tumour is in a limb then 'limb preservation surgery' is usually possible. Limb preservation surgery is where the surgeon can remove the tumour without amputating a limb or reducing the limb's function too much.

Surgeons have developed many ways to protect the function of limbs, the main one being replacement of the affected bone with a metal implant and a false joint.

Another technique is to carry out an autologous bone graft. This where healthy bone is taken from another part of the body to replace the bone that has been removed or damaged by the tumour.

Even with these advances in surgery around 10 per cent of patients require an amputation (removal of the limb) to safely remove the tumour.

Tumour removal from places other than the limbs (such as the spine or pelvis) can be very complicated and requires very careful individual planning for each patient.

Phase 3 - Pathology

When the tumour is removed by the surgeon, it is examined under a microscope by the pathologist. This is to check whether the tumour has been completely removed and to find out how much of the tumour has been killed by the chemotherapy. The results of this examination will help to provide information about how the patient is responding to treatment and to inform the next phases of treatment after surgery.

Phase 4 - Adjuvant Chemotherapy

Following surgery, patients will go on to receive further chemotherapy courses. Once again, the number of drugs and length of treatment may be different from country to country. Most treatment courses last for a further 16 -30 weeks after surgery.

In the UK, Ireland, much of Europe and the USA, current standard treatment is made up of the same 3 drugs and lasts for 18 weeks after surgery. Chemotherapy given after the surgery is known as adjuvant chemotherapy.

Phase 5 - Surgery to remove secondary tumours, if they are present (only in some patients)

If there is evidence that the tumour has spread to other parts of the body then an oncologist and surgeon may want to think about the possibility of removing the secondary cancers by surgery.

The doctor (oncologist) is the best person to describe treatment choices. Doctors will also tell patients what to expect from the treatment. Treatment of cancer involves patients and the doctors working together to find a care or treatment plan that fits their needs.

Treatment: In Detail

Chemotherapy

In most cases, chemotherapy for spindle cell sarcoma is used before surgery to start to kill the cancer cells within the primary tumour. Chemotherapy can also sometimes shrink the tumour to make it easier for the surgeon to remove it during surgery and kill any cancer cells that have escaped from the bone tumour and are floating in the blood (called micrometastases). It is also used after surgery to kill any remaining cancer cells that might have been left behind after surgery and to kill any cancer cells in the rest of the body.

Chemotherapy may be given as part of a clinical trial - a study used to investigate new or different treatments or side effects of treatments. Your MDT will let you know about any clinical trials that are available to you and ask whether you would like to take part.

In some patients, chemotherapy is given to help slow down the growth of the tumour and decrease pain and other symptoms when their cancer is very advanced and unable to be cured. This is known as palliative chemotherapy.

The chemotherapy drugs accepted as the best initial treatment for spindle cell sarcoma are:

• Methotrexate (M)
• Doxorubicin (other known as Adriamycin - A)
• Cisplatin (P)

This regime of drugs is commonly referred to as 'MAP' chemotherapy.

Other chemotherapy drugs that can be used, most commonly if the cancer returns or if the other drugs are not well tolerated, include:

• Ifosfamide
• Etoposide
• Gemcitabine
• Docetaxel

How chemotherapy works

Chemotherapy (or 'chemo' for short) is the name for drugs used for the treatment of cancer. These drugs kill cancer cells or stop their growth by interfering with the way cells divide and grow (also known as the cell cycle), or by damaging the cell's DNA (genetic code instructions).

Cancer cells are different to healthy cells because the cancer cells divide very rapidly. This fact is exploited by chemotherapy drugs, which target only rapidly dividing cells. Different chemotherapy drugs achieve this by targeting slightly different parts of the machinery that makes cells divide, and so often these different drugs are used together in combinations, to hit different parts of the cancer cell at the same time. This is called combination chemotherapy.

Most healthy cells do not divide very rapidly. However, some types of healthy cells in the body do divide rapidly, and these include hair follicle cells, skin cells, bone marrow cells, and the cells lining the digestive system. This means chemotherapy drugs can also affect these healthy quick-dividing cells and this is what causes the side effects that are associated with chemotherapy treatment.

Side effects can be unpleasant, such as nausea, diarrhoea, hair loss, mouth sores, an unusual taste in the mouth and tiredness (fatigue). Medications can be given before and after chemotherapy to help with some of these side effects.

• One former osteosarcoma patient, Megan Blunt, has written a book filled with tips on how to cope with chemotherapy. This book is called Chemotherapy, Cakes and Cancer is available to download as a PDF published by CLIC Sargent

How is chemotherapy given?

There are different ways patients are given chemotherapy: tablets, liquid medicine, injection or directly into the blood.

When a patient is given chemotherapy directly into their blood, the drug is given through a cannula (venflon), which is a flexible thin plastic tube that sits in a vein in the arm or hand. Alternatively, patients may have a central line, PICC (peripherally inserted central catheter) or implantable ports (Portacath®).

Portacaths®, PICCs and central lines can be kept in for weeks or even a few months. These lines enable the number of needles required during treatment to be minimised and more than one drug or treatment (such as fluids or nutrition) can be given at the same time because the lines can have multiple openings or 'lumens'.

Because central lines, PICCs and Portacaths® are all slightly different; the decision on which type of line will best suit the patient will be discussed by the nurses and the doctor in the medical team.

Figure 1(a). A central line, also known as a Hickman line. Image Courtesy of The Christie NHS Foundation Trust.

Figure 1(b). Peripherally Inserted Central Catheter (PICC). Image Courtesy of The Christie NHS Foundation Trust.

Figure 1(c). Implantable Port, (Portacath®). Image Courtesy of The Christie NHS Foundation Trust.

The chemotherapy drugs enter the blood through the cannula by an infusion usually called a drip. An infusion or drip is a method of giving a set amount (dose) of I.V. (Intravenous) medications such as chemotherapy over a set period. This period can be hours or days. The infusion can also be controlled by an infusion pump, which is connected to a central line or a PICC line. Some of the pumps are small enough to fit in a pocket meaning that patients can use them at home.

Chemotherapy is given in 'cycles.' A cycle is the treatment time plus a resting time. For example, a patient may be given a combination of chemotherapy drugs over 3-4 days and then there may be a resting period of 2½ weeks. Therefore, the cycle is 3 weeks long. The resting period helps the healthy cells of the body to recover before the next treatment cycle begins.

Surgery

Surgery is used to remove the primary tumour so that it can't grow or spread anymore. For most patients, limb sparing surgery is possible. This is complex surgery, which aims to keep as much normal function in the limb as possible. If a joint has to be removed patients may be supplied with a prosthetic (artificial) joint. Another surgical technique that is sometimes used is an autologous bone graft. This where healthy bone is taken from another part of the body to replace the bone that has been removed during surgery or damaged by the tumour.

Other surgical techniques include:

• resection alone (where only the tumour is removed)
• allografts (which use non-self tissue to replace damaged bone)
• irradiation/reimplantation (where the damaged bone is removed and treated with radiation to kill any cancer cells, before being put back into its original place in the body).

Very occasionally, because of the position or size of the tumour, the surgery involves removal of the whole limb (amputation). If possible, a prosthetic (artificial) arm or leg can be made for the patient. Amputation may also be needed if the cancer has spread to major blood vessels or nerves or if the patient develops a bad infection or other serious complication after limb sparing surgery.

Not all osteosarcomas are found in the limbs. Tumours from the pelvis, skull, spine and jaw can be difficult to remove completely by surgery. Radiotherapy is used occasionally in special situations where it is not possible to remove the whole tumour surgically.

Surgery may also be used to remove secondary tumours in the lungs.

Surgery may be needed in the future if the reconstruction of the limb wears out or if the tumour comes back.

Radiotherapy

On some occasions, radiotherapy may be used after surgery as an extra measure to ensure all the tumour cells in the area are destroyed.

Radiotherapy may be required if the patient has not responded well to surgery, or if the surgery was difficult and not all of the tumour could be removed. In these cases, radiotherapy is known to largely reduce the risk of the tumour returning at a later date(1,4,9).

Radiotherapy may also be used in patients with poor health who may not be fit to undergo surgery or require treatment that manages the symptoms of the cancer - which is known as ‘palliative radiotherapy’.

Ultimately, it is highly beneficial to diagnose and treat ameloblastomas as early as possible. Early diagnosis and adequate treatment leads to an excellent outlook for patients in previously reported ameloblastoma cases. The recurrence rate for ameloblastoma is approximately 50-72% if the tumour is not fully removed during surgery, emphasising the importance of correct diagnosis and an adequate surgical procedure(4).

It is important to bear in mind that patients receiving treatment outside of the UK may receive different tests and treatment plans in accordance to the treatment guidelines set out in that specific country. If you have any questions, please discuss this with your medical team or contact The Bone Cancer Research Trust for more information.

Key References:

1. Athanasou, N, Bielack, S, De Alava, E, Dei Tos, A.P, Ferrari, S, Gelderblom, H, Grimer, R, Sunday-Hall, K, Hassan, B, Hogendoorn, P.C.W, Jurgens, H, Paulussen, M, Rozeman, L, Taminiau, A,H,M, Whelan, J, Vanel, D. Bone Sarcomas: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Annals of Oncology. 2010; 21(5): v204-v213. Available at: http://annonc.oxfordjournals.org/content/21/suppl_...

2. Kitay, A, Rybak, L, Desai, P, Villalobos, C,E, Wittig, J,C. Primary Leiomyosarcoma of the Proximal Tibia: Case Report and Review of the Literature. Bulletin of the NYU Hospital for Joint Diseases. 2008; 66(1):49-53. Available at: http://www.tumorsurgery.org/portals/0/pdf/publicat...

3. Grimer, R.J, Docker, C, Spooner, D. Primary Spindle Cell Sarcoma of Bone – An Assessment of Outcome. Orthopeadic Proceedings. 2003. Available at: http://www.bjjprocs.boneandjoint.org.uk/content/85...

4. Chen, K-H, Chou, T-M, Sheih, S-J. Management of Extremity Malignant Fibrous Histiocytoma: A 10-year Experience. Formosan Journal of Surgery. 2015; 48(1): 1-9. Available at: http://www.sciencedirect.com/science/article/pii/S...

5. Malawer, M.M, Helman, L.J, O’Sullivan, B. Devita, Hellmans, and Rosenberg’s Cancer: Principles and Pathology. Section Two: Sarcomas of the Bone. Volume Two: Eighth Edition. 2008. Lippincott, Williams and Wilkins. Philadelphia. Available at: http://sarcoma.org/publications/articles/devita.pd...

6. Brewer, P, Sumathi, V, Grimer, R, J,Carter, S,R, Tillman, R,M, Abudu, A, Jeys, L. Primary Leiomyosarcoma of Bone: Analysis of Prognosis. Sarcoma. 2012. Available at: http://www.hindawi.com/journals/sarcoma/2012/63684...

7. Horvai, A, Krishnan Unni, K. Premalignant Conditions of Bone. Journal of Orthopaedic Science. 2006; 11(4): 412-423. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC278064...

8. Tomasik, P, Spindel, J, Miszczyk, L, Chrobok, A, Koczy, B, Widuchowski, J, Mrozek, T, Matysiakiewicz, J, Pilecki, B. Treatment and Differential Diagnosis of Aneurysmal Bone Cyst Based On Our Own Experience. Ortopedia Traumatologia Rehabilitacja. 2009; 11(5): 467-475. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19920289

9. Hsu, H-C, Huang, E-Y, Wang, C, J. Treatment Results and Prognostic Factors in Patients with Malignant Fibrous Histiocytoma. Acta
Oncologica. 2004; 43(6): 530-535. Available at: http://www.tandfonline.com/doi/pdf/10.1080/0284186...

10. Dasari. S, Tchounwou, P,B. Cisplatin in Cancer Therapy: Molecular Mechanisms of Action. European Journal of Pharmacology. 2014; 5: 364-378. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC414668...

Further Reading:

Nooji, M,A, Whelan, J, Bramwell, V,H, Taminiau, A,T, Cannon, S, Hogendoorn, P, C, Pringle, J, Uscinska, B,M, Weeden, S, Kirkpatrick, A, Glabbeke, M, Craft, A,W. Doxorubicin and Cisplatin Chemotherapy in High-Grade Spindle Cell Sarcomas of the Bone, other than Osteosarcoma or Malignant Fibrous Histiocytoma: a European Osteosarcoma Intergroup Study. European Journal of Cancer. 2005;
41(2): 225-230. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15661546