Chondrosarcoma

Chondrosarcoma is the most common form of primary bone cancer affecting all age groups.

Chondrosarcoma can affect people of all ages but is mostly found in adults between the ages of 30 and 60 years. 80% of cases are in people aged 40 years or older.

In the UK there are around 190 new cases of chondrosarcoma diagnosed each year. In The Republic of Ireland there are around 12 new cases of chondrosarcoma diagnosed each year.

The incidence rate in England is around 2.9 people affected per 1 million people of the population.

The different types of chondrosarcoma affect different individuals. These are:

Conventional chondrosarcoma

Mostly found in adults over the age of 50 years.
Affects males slightly more than females.
Accounts for 75% of all chondrosarcoma cases.

Dedifferentiated chondrosarcoma

The average age at presentation is between 50 and 60 years.
Males and females appear to be affected equally.

Mesenchymal chondrosarcoma

This can occur at any age, but it has peak incidences in teens and young adults.
Males and females appear to be affected equally.

Clear cell chondrosarcoma

This can occur at any age, but peak incidence is in 30s and 40s.
Males are more commonly affected than females (~ 2.5: 1).

There are four types of primary chondrosarcoma. They range from slow-growing non-metastasising lesions, to very aggressive metastasising tumours.

Conventional chondrosarcoma

Most chondrosarcomas (around 75% of cases) are called conventional chondrosarcomas.

Conventional chondrosarcomas are further classed based on their appearance under a microscope. Pathologists examine the cells in a biopsy of the tumour and examine the size of a structure within the cells called the nucleus. The pathologist assigns the grade of the tumour to say how different the cells look from healthy cells

Low grade (Grade 1): Most cells look like normal cartilage, some cells may have two nuclei.
Intermediate grade (Grade 2): Cell nuclei are misshapen, fragmented, or bigger than in low grade tumours. Intermediate tumours are treated in the same way as high grade tumours.
High grade (Grade 3): Cells of the same type have different shapes, lots of cells are in the process of division (mitosis), giant cells and many dead cells (necrosis) can be seen.

Grade 1 tumours are less aggressive than grades 2 and 3 tumours, meaning that grade 1 tumours are easier to treat. Most patients have low or intermediate grade conventional chondrosarcomas although rarely, conventional chondrosarcomas can be high grade.

Conventional chondrosarcomas can affect any bone. Most conventional chondrosarcomas arise from inside the bone; however, around 15% arise from cells on the surface of the bone. Conventional chondrosarcomas are equally likely to appear in the central part of skeleton as in the bones of the limbs. The thigh bone (proximal femur) is the most frequently affected followed by upper arm bone, distal femur, and ribs.

Dedifferentiated Chondrosarcoma

Around 10% of chondrosarcomas are dedifferentiated chondrosarcoma.
They are high grade and very aggressive.
The most common sites affected are the thigh (femur) and pelvis.

Mesenchymal Chondrosarcoma

This is a very agressive form of chondrosarcoma. It is extremely rare and accounts for less than 2% of chondrosarcomas.
It can occur anywhere in the body - either in the bones or in soft (non-bony) tissues.
If the tumour first appears in non-bony tissue it is described as 'extra-skeletal', which means 'outside the bones'.
Around 70% of mesenchymal chondrosarcomas originate in bone, while 30% are extra-skeletal.
Cells of the tumour may look like cells of Ewing's sarcoma, a different bone tumour.

Clear Cell Chondrosarcoma

These low grade tumours are extremely rare, accounting for less than 2% of chondrosarcomas.
This type of chondrosarcoma tends to occur in the long bones of the arms and legs.
The inside of the cells (cytoplasm) appears clear/ empty under the microscope.

The type of treatment a patient receives will depend on which type of chondrosarcoma is diagnosed.

The main treatment for chondrosarcoma is surgery to remove the tumour. Radiotherapy is sometimes used, and much more rarely chemotherapy might be used.

Chondrosarcoma can be described using different classifications. This helps doctors decide how best to treat the tumour.

Tumours are classed as primary or secondary.

Primary chondrosarcomas start from cells in a healthy bone.
Secondary chondrosarcomas arise from a benign tumour that is already present in the bone. These benign tumours include enchondroma and osteochondroma.

The location of the tumour in the bone. Chondrosarcomas can be either:

Central, meaning inside the bone cavity.
Surface, meaning on the outer surface of the bone and sometimes described as periosteal. Peripheral chondrosarcomas are surface chondrosarcomas that are secondary to osteochondroma.

When the tumour is examined under a microscope, differences can be seen between some tumour types. This classification is called the 'histological variant'.

Chondrosarcoma should not be confused with 'chondroblastic osteosarcoma'. This is a bone-forming tumour, but the tumour cells also form cartilage. The treatment for chondroblastic osteosarcoma is the same as for osteosarcoma, not chondrosarcoma.

There has been a lot of research into possible causes of chondrosarcoma but the underlying cause remains unknown in most cases.

It is known that cells contain important information in their chromosomes called genes, which help them to divide and grow normally. Damage to these genes in one single cell can cause the cell to behave differently and grow abnormally, which can then lead to development of cancer.In chondrosarcoma, there is damage to the cell's genetic information such as abnormalities of genes (mutations) called tumour suppressor genes and oncogenes as well as genes which control the copying of the cell's DNA. We do not know why the damage occurs in most cases.In some young patients we know that chemotherapy or radiotherapy for another tumour can damage the DNA enough to cause chondrosarcoma.

Some recent research has identified a pair of genes that are frequently damaged in chondrosarcoma tumours. Researchers looked in cells from many different chondrosarcoma tumours and found that two genes, called IDH1 and IDH2, were damaged (mutated) in many tumours. These genes are also found to be damaged in some other cancer types. We don't know why these genes get damaged but we do know that the damage is not inherited.

A small proportion of patients are known to have inherited damaged genes from their parents. This is known as a genetic predisposition, which means they have an increased risk of developing different types of cancer, including chondrosarcoma.

Doctors and scientists all over the world are involved in research to try to understand the difference between normal bone cells and chondrosarcoma cells. This may enable them to find treatments that can target the abnormal chondrosarcoma cells rather than normal cells in the body.

The risk factors for chondrosarcoma

Although doctors do not yet fully understand what causes chondrosarcoma, there are several factors that put people at a higher risk. A risk factor is something that can increase the chance of getting an illness.

General risk factors

Gender: Males have a slightly higher risk compared to females.
Age: Most chondrosarcomas develop in people over the age of 40.
Underlying bone diseases: Bones which already have something wrong with them (underlying bone abnormalities) are at a higher risk of gettingn chondrosarcoma. These diseases are very rare:
- Paget's Disease is a disease that makes bones painful and encourages bone cells to divide more rapidly.
- Ollier's Disease is a condition in which benign tumours in the bones cause the affected bones to swell. The condition usually presents before the age of 10. Patients with Ollier's Disease have around a 20-25% chance of developing chondrosarcoma. Many Ollier's Disease patients have mutations in IDH1 or IDH2 genes.
- Maffucci Syndrome is a rare disorder that gives people with this condition a 20-25% risk of developing chondrosarcoma. Many Maffucci Syndrome patients have mutations in IDH1 or IDH2 genes.

Inherited risk factors

These are risk factors that people inherit from their parents and have from birth (hereditary). They can be passed on from one or both parents. The risk is passed to the child through the parent's genes. So, just as children inherit features such as hair or eye colour from their parents, a very small number can inherit a risk that will increase their chance of getting chondrosarcoma.

Certain hereditary conditions may make people more susceptible to chondrosarcomas:

Multiple hereditary exostoses (hereditary skeletal disorder): Patients with this condition have a 0.6% to 2.8% risk of developing chondrosarcoma.
Wilm's tumour (kidney tumour): In extremely rare cases, chondrosarcomas have been seen as secondary tumours from a primary Wilm's tumour.

Environmental risk factors

Treatment by radiation or chemotherapy for a pre-existing condition: People who have received radiotherapy for cancer before have a slightly higher chance of developing chondrosarcoma.

The most commonly-reported symptoms of chondrosarcoma are:

Localised pain. This can be dull in nature, occurring when a patient is at rest, and may become worse at night. Pain may also become progressively worse.
Local swelling.
Walking with a limp or having restricted movement of a joint (if near the affected bone).

These symptoms can be present alone or in combination. These symptoms are often of long duration, possibly several months or years. The average duration of symptoms before diagnosis is thought to be between 1 and 2 years.

20-30% of chondrosarcomas are painless and may only be found when a patient suffers with a fractured bone caused by a mild injury, such as from a minor fall or accident. The fracture can happen where the bone has been weakened by the tumour. This is known as a pathological fracture.

Around 50% of patients with spinal chondrosarcoma will experience neurological symptoms, which result from the tumour pressing on the nerves in the spine. This can include pain, numbness or tingling, muscle spasms or even muscle weakness.

The symptoms of chondrosarcoma are all common to other conditions, which makes it hard for doctors to reach the correct diagnosis.

The most common clinical signs are:

A mass that can be felt (palpable) when undergoing physical examination.
Broken bone (fracture).

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 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 sarcoma 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 sarcoma 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 cancer 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 sarcoma 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

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 one of two types:

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.

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):

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 sarcoma 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.

What kind of treatment is used for chondrosarcoma?

The main and still the most successful treatment option for chondrosarcoma is surgery to remove the tumour (surgical resection).

For higher-grade tumours, such as dedifferentiated or mesenchymal chondrosarcomas, which are at higher risk of recurrence and spread (metastasis); adjuvant therapies such as radiotherapy, chemotherapy or proton therapy may be used.

Surgery

The aim of surgery is to remove every last cell of the primary tumour. This prevents the tumour from growing back later, which is called a local recurrence, or spreading to another part of the body, which is called metastasis. The surgeons aim to remove the entire tumour safely and at the same time try to keep the body working as normally as possible.

Surgery for low grade chondrosarcoma

Low grade chondrosarcomas can be treated by different surgical techniques: either a wide resection (which involves cutting out the tumour plus the tissue directly next to the tumour) or a procedure called curettage (which involves scraping the tumour cells out of the bone) followed by adjuvant treatment such as cryosurgery (which means using liquid nitrogen to freeze out any remaining cancer cells), or high speed burring of the cavity.

Reconstruction of the bone defect depends on which bone is involved and the preference of the surgical team, but may involve the use of:

Allograft bone - using donated bone to repair the patient's bone after surgery.
Autologous bone - this is when bone is taken from another part of the patient's body to replace the bone that has been removed during surgery.

Surgery for high grade chondrosarcoma

The type of surgical procedure will depend on the size and location of the tumour. The aim of the surgery, where possible, is to remove the entire tumour along with a wide margin of the surrounding healthy tissue (wide resection). For some tumours it may be possible to remove the tumour without having to reconstruct the bone and losing too much function.

For important bones such as the femur or pelvis, the surgery may include complex site-appropriate reconstruction of the bone using:

Endoprosthetics - metal implant in the bone or a false joint.
Allograft bone - using donated bone to repair the patient's bone after surgery.
Autologous bone - this is when bone is taken from another part of the patient's body to replace the bone that has been removed during surgery.

Removing tumours can be very complicated, and requires very careful individual planning for each patient.
If the tumour is in the spine or base of the skull, it is much more difficult to remove without damaging the spine or brain. In these cases radiotherapy may be used where it is not possible to remove the whole tumour surgically.

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.

Radiotherapy

Radiotherapy is not very effective as a treatment in the majority of patients with chondrosarcoma.

However, there are times when radiotherapy is used:

When chondrosarcomas are difficult to remove surgically
As a treatment for mesenchymal or dedifferentiated chondrosarcoma
To decrease pain and discomfort when a patient's cancer is advanced and unable to be cured. This is known as 'palliative radiotherapy'.

Chemotherapy

Chemotherapy is not usually used as a treatment for chondrosarcoma, as the tumours are resistant to the chemotherapy drugs, meaning that chemotherapy is not effective.

However, chemotherapy is sometimes used for patients with mesenchymal or dedifferentiated chondrosarcoma, as these tumour sub-types seem to respond better than conventional chondrosarcomas. The chemotherapy drugs that can be used in this treatment include doxorubicin and cisplatin.

Although these drugs are sometimes used, it is not yet clear whether these treatments have an effect on outcome. This is largely because the very small numbers of these forms of chondrosarcoma make it difficult to study.

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

Proton beam therapy

Proton Beam Therapy (PBT) is a type of radiotherapy that uses beams of 'protons' (energised particles), instead of beams of X-rays (photons), that are used in conventional radiotherapy. It is more targeted than conventional radiotherapy so does less damage to the healthy tissue surrounding the tumour and other organs. This is advantageous for some primary bone cancers where the cancer is close to a critical part of the body such as the base of the skull, spinal cord or other critical structures or nerves.

What is the difference between PBT and radiotherapy?

As proton beam therapy is highly targeted towards the tumour, it means it is often possible to treat areas closer to very sensitive structures such as the spinal cord.

Overall, this means that fewer healthy cells nearby receive a dose of radiation. This is particularly important in children, whose bodies and structures are still developing.

Who might benefit from it?

The main advantage of PBT is that it can deliver a more targeted use of radiotherapy than x-ray radiotherapy.

This is particularly beneficial to children and young adults with a primary bone cancer, as it avoids damaging healthy, developing tissues and is thought to reduce the risk of secondary malignancies later in life.

For adults, it is considered beneficial for tumours in areas where surrounding tissue is highly sensitive to the effects of radiation. For example, primary bone cancers in a sharply defined areas are often suitable for PBT i.e. a chondrosarcoma of the base of the skull.

Side effects?

One of the key advantages of proton beam therapy over conventional radiotherapy is that it is more targeted. It does less damage to the healthy tissue around the tumour and the rest of the brain. This means it causes fewer side-effects, however, there are a few side-effects which are not uncommon.

The following side-effects are usually temporary and often disappear after treatment has finished:

fatigue
redness that resembles sunburn - this can appear in the area where the proton beam was directed
hair loss.

How can I access PBT?

PBT is now available in UK through NHS. There is an NHS Centre at the Christie Hospital, Manchester as well as a second NHS PBT Centre planned for University College Hospital London (UCLH) due to open soon in 2021.

Costs involved

All PBT is approved by the Proton Clinical Reference Panel. The NHS will cover the cost of PBT treatment at approved treatment centres, whether in the UK or in the USA, Germany and Switzerland. If sent abroad for PBT, it will also fund economy travel and approved accommodation for the patient (children) and one to two carer(s)/parent(s) and one parent/carer for teenage and adult patients, accompanying them.

The NHS will not fund any meals or refreshments, nor any upgrades to travel or accommodation. If you need help to cover travel costs not subsidised by the NHS, contact our Support & Information Service about our Travel Assistance Grant and other financial help that may be available.

Targets for novel treatments

Research is needed to find better treatments for chondrosarcoma because chemotherapy and radiotherapy are not normally effective on these tumours. Also we don't know what makes chondrosarcoma recur (come back again) in some patients, or metastasise (spread to other organs).

If scientists and doctors can better understand why chondrosarcoma is resistant to chemotherapy and radiotherapy, their research may reveal new targets for treatment or adjuvant treatments to surgery.

One area of research that is currently underway is a series of investigations into a gene network called the "hedgehog pathway" (named after Sonic the Hedgehog, a computer game character). This network of genes is part of the machinery that works inside cells to control cell division. Researchers have found that chondrosarcoma cells in the laboratory stop growing when the hedgehog pathway is switched off. A phase 2 clinical trial of a new drug that targets the hedgehog pathway in chondrosarcoma has recently been carried out in the USA and if the outcomes from this trial are positive then wider trials may follow.

Why chondrosarcoma is resistant to chemotherapy and radiotherapy

Chemotherapy and radiotherapy target rapidly dividing cells. The majority of chondrosarcomas are low grade (grade 1) and are therefore relatively slow-growing; this makes them resistant to chemotherapy and radiotherapy.

In addition, some chondrosarcomas express a gene called 'P Glycoprotein,' which is normally found in intestinal tissues, and in the brain. P Glycoprotein exists in healthy tissue to pump poisons out of cells. If P glycoprotein gets switched on in cancer cells it pumps chemotherapy drugs out of the tumour, rendering the drugs ineffective.
P glycoprotein is effective against many different drugs and so is a big barrier to cancer treatment.

Chondrosarcomas also tend to have a very poor blood supply meaning that it is difficult for drugs to reach the tumour cells.

Radiotherapy resistance (radioresistance) in chondrosarcoma is caused by the loss of certain genes that are the targets of radiation.

In normal cells, radiation damage to a cell causes very reactive molecules called 'reactive oxygen species' or ROS to be produced. These ROS can damage or break the cell's DNA, which damages the cell's genes. DNA damage in the cell results in the activation of 'tumour suppressors,' which are proteins that either repair the damage or start cell suicide (apoptosis) to prevent the genetic damage being passed on when the cell divides. If any of the functions that are needed to recognise the damage and act on it are missing in the cancer cell then they will be radioresistant (resistant to radiotherapy).

Loss of particular genes known as tumour suppressor genes has been shown to make cancer cells radioresistant. For example the loss of the tumour suppressor gene called P16. In around half of high grade chondrosarcomas, there is damage to P16.

There may also be increased amounts of proteins in chondrosarcoma cells which prevent the cell from committing suicide or apoptosis (Ay-POP-tow-ciss) in response to the radiation. These are called anti-apoptosis proteins. Chondrosarcoma cells have been shown to have higher levels of the anti-apoptotic proteins called Bcl-2 and XIAP and Survivin.

All these research findings can suggest targets for novel and specific treatments against chondrosarcoma. For example, if the gene for Bcl-2 can be silenced or 'switched off,' the cell may respond to the radiation.

The Bone Cancer Research Trust is actively involved in funding research, especially translational research to help to find new treatments. Translational research is research that bridges the gap between promising findings in the laboratory from basic research and their clinical use in patients.

Prognosis

The word 'prognosis' refers to what doctors think the chances are of the patient's cancer being cured with treatment or the likelihood of it returning. This depends on many different things, which vary between different patients.

In general, the prognosis for chondrosarcoma depends on:

The stage of disease at the time of presentation, whether it is localised or metastatic (spread), or recurrent (come back).
The grade of the chondrosarcoma (how abnormal the cells look).
The type of chondrosarcoma - dedifferentiated chondrosarcoma and mesenchymal chondrosarcoma are more aggressive than conventional chondrosarcoma.
Location of tumour, axial skeleton (skull, spine, pelvis) tumours may be more difficult to treat than tumours in the limbs.
Adequacy of surgery.
Whether lung (pulmonary) metastases can be removed with surgery (resectable).

Doctors cannot be absolutely certain about a patient's prognosis because each patient and each cancer can behave differently.

Follow-up care

After finishing treatment, chondrosarcoma patients require follow-up care. Outpatient hospital visits will be needed on a regular basis for the first few years after treatment, and then yearly after that.

These visits help the clinical team to keep an eye on a patient's general health as well as an opportunity to carry out some tests. These tests are very important because they can show up any 'late effects' from the cancer treatment. Most centres encourage patients to get in touch if they have problems between appointments.

Follow up care with an orthopaedic surgeon also helps to look out for surgery-related complications and to make sure the limb is working well.

Reaching the end of treatment can bring about mixed emotions - the thought of having no more treatment can be a cause for celebration, but this can be mixed with anxiety for the future. Many emotions can arise surrounding the process of returning to a 'normal' life after cancer.

The issues encountered after treatment can be complex and include workplace and financial issues. Macmillan Cancer Care provides a wealth of useful information on living with and after cancer.

Relapse and metastases

In some patients, the cancer returns after treatment.

'Relapse' means that the cancer has returned. This can be in the same bone or area as the original cancer (local relapse) or in a different place, often in the lungs (metastasis).

If the cancer returns it will require further treatment. This treatment may involve more surgery, or possibly radiotherapy or chemotherapy. Your doctor will be able to advise you about which treatments are necessary.

What are late effects?

The surgical treatment of chondrosarcoma can involve major surgery and this can affect patients' long-term mobility. Some patients who have surgery in the pelvis may need to use a stick or crutches for walking. Patients will work together with physiotherapists and occupational therapists to improve their mobility and independence after such surgery.

Most patients experience side effects during their treatments which go away or improve after treatment is ended. However, some side effects become permanent or develop months or years after treatment has ended. These are known as late effects of cancer treatment. More is becoming known about late effects as people are living longer after being treated for cancer.

The late effects of cancer treatment vary depending on the type of cancer, the treatment and surgeries and the age of the patient when undergoing treatment.

However, not everyone who has cancer treatment will necessarily experience late effects. Different chemotherapy drugs cause different late effects and late effects of radiotherapy and surgery will affect only the area of the body exposed to them.

Signs and Symptoms of Late Effects

You can talk to your doctor or CNS about the late effects of your particular treatment or surgery. They should be able to advise you on which late effects you are at risk from. However, the late effects of many cancer treatments still often go undiagnosed.

At your follow-up appointments you will be screened for late effects of your cancer treatment and surgery. It is also an opportunity to talk to your doctor about any signs or symptoms you may be suffering from and to discuss whether these are late effects.

If you were treated for cancer many years ago or are no longer having follow-up appointments, you should talk to your GP about late effects or contact a Late Effect Clinic.

Late Effects Clinics

If you had your cancer treatment as a child you will be monitored for late effects by your oncology team or a late effects clinic specifically for those patients treated as children.For all other cancer patients, they will be screened by their oncologist whilst under their care but are no longer monitored once they are discharged by their oncology/surgical team.

In September 2014, a late effects clinic was established at Nottingham City Hospital.This Late Effects Clinic is a bespoke service which aims to support people suffering with long-term effects from radiotherapy and chemotherapy and offers practical advice and signposting for a range of physical and psychological effects. It offers a wide range of support and guidance regarding late effects such as bowel and bladder problems, infertility, osteoporosis, sexual dysfunction, pain management and psychological issues to name a few. Patients self-refer and it is open to all patients who are a minimum of 6 months out of treatment. There is no upper limit on time from finishing treatment.

Since this clinic was established, similar clinics have been set up in Derby, Sheffield and Taunton and many more are developing throughout the country.

There is also a Complex Cancer Late Effects Rehabilitation Service based at The Royal National Hospital for Rheumatic Disease in Bath which is a two-week inpatient rehabilitation service for those patients with complex, chronic late effects. Referral to this service is via the late effect clinic or local pain services.

You may find our webinar on the Late Effects Clinic with radiographer, Emma Hallam helpful.

The Bone Cancer Research Trust's information has been compiled using only peer-reviewed clinical and scientific studies, reviews and case studies. Peer-review is a process in which the work of one scientist or doctor is looked at and checked by other experts in the same subject area. The peer-review process helps ensure the science is 'reliable'.

If you are interested in reading deeper into the subject, we have provided a bibliography listing the references and books we used to compile our information about chondrosarcoma.

Books

Alberts B, Johnson A, Lewis J, Raff M. Molecular Biology of the Cell. Garland Science; 5th edition, 2005. ISBN-10: 0815341059.
Bernsein ML, Lewis I. Osteosarcoma in, Education Book, International Society of Paediatric Oncology, 37th Congress of the International Society of Paediatric Oncology Vancouver, British Columbia, Canada, September 20-24, 2005, Section B, Chapter 6, p. Available to download here.
Cullinane CJ, Burchill SA, Squire JA, O'Leary JJ, Lewis IJ (eds). Molecular Biology and Pathology of Paediatric Cancer. Oxford University Press. ISBN-10: 0192630792.
Kleihues P, Sobin L, Fletcher C et al, (eds.) WHO Classification of Tumours: Pathology and Genetics of Tumours of Soft Tissue and Bone, Lyon, France: IARC Press. PDF version available free here.
Mackay J. The chemotherapy and radiotherapy survival guide. New Harbinger Publications, 1998. ISBN 1572240709.

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