Osteosarcoma can affect people of all ages but is mostly found in older children, teenagers and young adults between the ages of 10 to 24.

There is also a smaller group of people over the age of 65 who develop osteosarcoma, peaking in those between the age of 70 to 74.

• In the UK around 160 people are diagnosed with osteosarcoma each year.
  This is fewer than 3 people out of every million people in the population. This is known as the 'incidence rate' (2.6 per 1,000,000 people).
• Around 11 cases of osteosarcoma are diagnosed in the Republic of Ireland each year.
• Osteosarcomas affect males slightly more than females (approximately 1.4 times more often).
• Osteosarcoma tends to occur at an earlier age in girls than in boys. This may be because girls have a growth spurt at a slightly earlier age.

Although there has been a lot of research into possible causes of osteosarcoma, we still don't understand what causes osteosarcoma in most cases. However, in 10-15% of people, a possible cause can be identified.

Information about what causes a disease is called 'aetiology'.

Risk factors

Inherited risk factors

• Genetic predisposition. Damaged genes can be inherited from a person's parents, making it more likely that a person will develop cancer. For example, Li-Fraumeni Syndrome which is an inherited predisposition to rare cancers due to a change (mutation) to the TP53 gene.
• Underlying bone abnormalities. Bones which already have something wrong with them are more likely to develop bone cancer, such as Paget's disease of bone. Around 0.1% of patients with Paget's disease of bone develop osteosarcoma.
• Retinoblastoma. This is a rare, inherited childhood eye cancer that usually occurs when a baby inherits a damaged copy of a gene called Rb1. In healthy cells this gene acts to stop cells dividing too quickly but if the gene is damaged then the chance of developing cancer increases. Children who have had retinoblastoma have a higher risk of osteosarcoma.
• Other rarer conditions have an increased risk of osteosarcoma. These include Rothmund-Thomson syndrome, which affects many parts of the body (slow growth, skin rashes, delayed bone formation and bones that do not form normally) and Werner's syndrome, which is a condition that starts around the same time as puberty and leads to the appearance of old age by 30-40-years old.

General risk factors

• Radiotherapy (radiation treatment) for cancer can damage the DNA in bone cells and cause the cells to become cancerous.
• Age: Osteosarcoma is more common in people between 10 and 24 years old. During adolescence, bones grow very quickly. It is thought that this rapid bone growth may be part of the reason why young people develop osteosarcoma more often during adolescence than younger children or older adults.
• Height: Research has shown that patients who develop osteosarcoma are more likely to be taller than people of average height. Osteosarcoma is also common in the long bones of tall dogs, such as Great Danes and Irish Wolfhounds. This may be further evidence of a link between rapid bone growth and osteosarcoma.
• Gender: Males have a slightly higher risk compared to females. This is likely due to the protective effects of oestrogen against cancer development although there is ongoing research into this.

Environmental risk factors

The only established environmental risk factor is from exposure to ionising radiation from previous radiotherapy treatment for cancer.

There has been research into other possible environmental risk factors such as exposure to pesticides and previous treatments with chemotherapy drugs, although no links have been shown. The Bone Cancer Research Trust funded research to investigate if there was an association between fluoride levels in drinking water and bone cancer incidence.

When doctors talk about 'presentation', they mean 'symptoms' and 'clinical signs'.

The most reported symptoms of primary bone cancer are:

• A mass that can be felt (palpable) when undergoing physical examination
• Broken bone (fracture) resulting from weakening of bone due to a tumour - a pathological fracture
• Bone pain which is worse at night, constant or intermittent, resistant to analgesia and may increase in intensity
• Easy bruising
• Mobility issues - an unexplained limb, joint stiffness, reduced range of movement
• Inflammation and tenderness over the bone or joint can be seen/felt if a tumour is near the skin. Swelling is not always visible because if a tumour is deep inside the body, such as in the pelvis.

Less common symptoms include:

• fever (known as pyrexia)
• tiredness or feeling weary (referred to as lethargy or fatigue)
• pain accompanied by tingling and numbness (pins and needles)
• weight loss and loss of appetite
• breathlessness

Symptoms vary from patient to patient, can range in their severity and there is no definitive list. Symptoms may be mild at first, presenting over a period of a couple of weeks, but they may appear suddenly. Some patients report their symptoms disappearing for relatively long periods before suddenly returning.

Symptoms may be present for weeks or months, sometimes even longer before patients are diagnosed. This can be because the symptoms of osteosarcoma are quite general and could indicate a number of conditions. Some examples of these in older children, adolescents and young adults include:

• Tendonitis - an inflammation of the tendons.
• Osgood-Schlatter disease - inflammation of the growth plate where the kneecap tendon inserts.
• Trauma - injury caused by something external e.g. a sports injury.
• Slipped epiphysis - where the growing section of a bone at the end of a long bone slips and moves on the bone, which can cause a lot of pain.

In younger children the same symptoms could indicate, amongst other conditions:

• Osteomyelitis - an infection of the bone.

As the symptoms are general and could be caused by other conditions, many patients struggle to get a correct diagnosis when they first see a doctor. Many patients experience pain that is intermittent, and this can mislead doctors into thinking that the cause of the pain is temporary. Most patients do not actually feel ill until the cancer is fairly well advanced.

When looked at under the microscope, all osteosarcomas can be seen to consist of abnormal cells that are 'trying' to make bone. By looking closely at what kind of cells are in the tumour, doctors can class each patient's osteosarcoma as one of several subtypes of osteosarcoma:

Osteoblastic Osteosarcoma

Usually, the cancer cells look like bone-forming cells. These cells are called osteoblasts and so this type of osteosarcoma is known as 'osteoblastic osteosarcoma.' Osteoblastic cells produce an osteoid matrix. This is the most common subtype of osteosarcoma (90% of cases).

Chondroblastic Osteosarcoma

Sometimes, the cells look different under the microscope. If the cancer is trying to make cartilage as well as bone then the tumour is called 'chondroblastic osteosarcoma.' Chondroblastic cells produce a cartilage-like matrix.

Fibroblastic Osteosarcoma

If there is only a small amount of bone being made by the cancerous cells then the tumour may be called 'fibroblastic osteosarcoma.' Osteosarcoma cells look "spindly" down the microscope, the tumour is highly vascular and does not much produce much osteoid.

Telangiectactic Osteosarcoma

If there are lots of abnormal blood vessels in the tumour as well as bone forming cells then the tumour is called 'telangiectatic osteosarcoma.' This type of osteosarcoma is very lytic and "eats" into the bone, leaving lots of small pockets that fill with blood.

Small Cell Osteosarcoma

Some osteosarcomas contain small round cells and are called 'small cell osteosarcoma.' These can sometimes be difficult to tell from other tumours, which contain small round cells.

Giant Cell Rich Osteosarcoma

Giant cell rich osteosarcoma (GCRO) is an uncommon variant which makes up about 3% of all osteosarcomas. It is characterised by an abundance of osteoclastic giant cells and lack of tumour osteoid. This leads to its confusion with a giant cell tumour (GCT), especially when it occurs in an epiphyseal location.

Periosteal Osteosarcoma

Periosteal osteosarcoma arises within the thick layer of tissue that immediately surrounds the bone, producing a cartilage-like matrix. This subtype is generally low grade.

Parosteal Osteosarcoma

This subtype usually occurs on the surface of the bone and looks very similar to fibroblastic osteosarcoma. These cases are low grade also, parosteal being the lowest grade of the two.

High grade and low grade - what does this mean?

All subtypes of osteosarcoma are treated in the same way. These osteosarcomas mostly start inside in the bone and are called 'high-grade'.

High grade means that when the cells of the tumour are looked at under a microscope, many cells are in the process of dividing. The tumour behaves in an aggressive manner, meaning that the cancer cells can invade surrounding healthy tissues and spread to other organs. As a result, the cells can spread to other sites in the body at an early disease stage.

Sometimes, osteosarcoma can start either on or close to the surface of bone. Some of these tumours have the same high grade appearance (cells are dividing rapidly) as the common subtypes above and are treated in the same way with a combination of surgery and chemotherapy drugs.

Other types can be low grade (less aggressive) and may require surgery alone. These are the parosteal or periosteal osteosarcomas. Low grade osteosarcomas are extremely rare and occur in less than 10 people per year in the UK.

Very rarely tumours which appear identical to osteosarcoma, can arise outside of the bone in unusual places. This is known as 'extraosseous osteosarcoma.' These are treated in the same way as conventional osteosarcoma; with a combination of surgery and chemotherapy if the tumour is of a high grade.

Going to the doctor

The symptoms of osteosarcoma are general. There is no one clear sign that doctors can easily look for to make a diagnosis of osteosarcoma.

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 is concerned about the patient's symptoms, there are national guidelines they should follow. According to the NICE Suspected Cancer: recognition and referral guideline (NG12)

• 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 surgical 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 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 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. For more information on X-rays please click here .

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 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.

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 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.

How is osteosarcoma treated?

Since the 1970s the survival rates for osteosarcoma have improved dramatically as treatments have been revolutionised using chemotherapy and improved surgical techniques.

During the 1980s the way osteosarcoma was treated became standardised throughout much of the world. The usual curative treatment for high grade osteosarcoma involves chemotherapy and surgery.

For information about survival rates for osteosarcoma please go to: How will Osteosarcoma affect me in the long term?

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 made by the MDT.

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 osteosarcoma 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 osteosarcoma 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

Current clinical trials for osteosarcoma

• ICONIC (NCT04132895): this is an observational longitudinal trial to collect clinical data and lab findings about patients of all ages with osteosarcoma in the UK. The purpose is to establish why osteosarcomas arise and grow, what makes it spread, and why some patients respond to treatment better than others. Genetic information on these patients will also be collected and analysed to inform about causes of osteosarcoma and characteristics of the disease that we can target with new treatments. The information is planned to be used to develop clinical trials of new treatments. The ICONIC trial is supported and run by Cancer Research UK and University College London (UCL) Cancer Trials Centre. More information here.
• OLIE (NCT04154189): multi-tyrosine kinase inhibitors such as sorafenib, regorafenib and apatinib have shown benefit in osteosarcoma in early phase trials. These drugs work by stopping cell communication that drives tumour growth. OLIE is a multicentre phase 2 study (second step in assessing a new drug in humans) comparing the efficacy and safety of a multiple kinase inhibitor. Lenvatinib in combination with ifosfamid (I) and etoposide (E) versus IE in TYA with relapse or refractory osteosarcoma. More information here.

We also advise you to enquire with an Experimental Cancer Medical Centre. There are different centres across the UK.

We encourage you to discuss any trials with your oncologist, having a printout to refer to at your next clinic/ telephone appointment.

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.

There are tips on some good websites about dealing with side effects such as mouth sores, skin care and coping with hair loss:

• Coping with hair loss: Teenage Info on Cancer (TIC) and Teenage Cancer Trust
• Mouth sores and eating problems: Teenage Cancer Trust and TIC and Macmillan
• 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.

Additional drugs

Mifamurtide marketed as Mepact, is a drug for osteosarcoma treatment - a type of immunotherapy. A clinical trial in the USA showed that the drug used alongside chemotherapy and surgery may improve long-term survival in patients with non-metastatic disease (no spread of the cancer). The drug stimulates a type of white blood cell in the patient's own immune system to attack the cancer cells. Mepact is given twice per week for 12 weeks and then once per week for the next 24 weeks.

Mepact is available for osteosarcoma patients in the UK and Ireland. It is suitable for patients aged 2-30 years who have already had surgery to completely remove their osteosarcoma, and whose disease is non-metastatic (the cancer has not spread).

The Bone Cancer Research Trust was active in supporting the approval of Mepact for patients in the UK and were consulted by NICE during the appraisal process.

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

Because osteosarcomas are not very sensitive to radiation, radiotherapy is not used very often for osteosarcoma.

Occasionally, in special circumstances, radiotherapy might be recommended to treat osteosarcoma following surgery. Also, radiotherapy might be used if surgery to remove the tumour is not possible.

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 spinal cord.

What is the different between proton beam therapy and radiotherapy?

As proton beam therapy is highly targeted towards the tumour, it means it is often possible to treat areas close 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 such as Ewing sarcomas, osteosarcomas of the spine or pelvis as well as chordomas are often suitable for PBT.

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 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.

For more information on proton beam therapy, click here.

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.

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 osteosarcoma depends on:

• The patient's age and general health
• The location and size of the osteosarcoma
• Results of tests; the grade and stage of the osteosarcoma (how abnormal the cells look) and whether it is localised or metastatic (spread), or recurrent (come back)
• How much of the cancer could be removed by surgery
• Response to treatment, for example, how effective was chemotherapy prior to 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.

The overall 5-year survival rate for osteosarcoma is around 50-55%.

The term 5-year survival rate can sound quite misleading and worrying to some people. However, the term does not mean people only lived for 5 years after diagnosis; it refers to the fact that 55 out of every hundred people with osteosarcoma are alive 5 years after their diagnosis. These people may not all be cured; some may be still be undergoing treatment.

Follow-up care

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

These visits will help 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.

The Children's Cancer and Leukaemia Group (CCLG) provide useful information for children and their parents about what to expect once treatment is finished.

Reaching the end of treatment can bring about mixed emotions. The thought of having no more chemotherapy can be a cause for celebration, but this can be mixed with anxiety for the future.

The CCLG's booklet End of treatment... What happens next? is for 10-16-year olds who have reached the end of their cancer treatment. The booklet deals with many of the emotional issues surrounding the process of returning to a "normal" life after cancer.

A second version of this booklet End of treatment - for parents is available for the parents of a child who has had cancer. This deals with many of the practical issues as well as emotions that might arise when a child reaches the end of their cancer treatment.

For adults who have had treatment for cancer, the issues can be more complex and include workplace and financial issues. Macmillan Cancer Care provides a wealth of useful information on living with and after cancer, which includes information and tips on a broad range of topics.

Relapse and metastases

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

If the cancer returns it will require more treatment. This will probably involve more chemotherapy and sometimes further surgery. The MDT will be able to advise you on which treatments are necessary. You may also find Maggie's information on the fear of cancer returning helpful.

Emotional effects

The experience of having cancer can be frightening and stressful, and so the emotional effects of cancer can be as severe as the physical effects.

The Children's Cancer and Leukaemia Group have produced a booklet for teenagers and young adults called After Cure which is full of helpful information for living well after having cancer.

Macmillan Cancer Care has some very useful pages for adults on coping with the emotional aspects of cancer.

Late effects

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.

If you were treated for cancer as a child, you may be at risk of the same late effects as people who were adults during their cancer treatments and additional late effects as children's tissues, organs and bones grow rapidly and cancer treatment can interfere with this critical time of growth.

As with late effects in adults, late effects from childhood cancer treatment will vary depending on the type of cancer and type of treatment. Additionally, the age at which you were treated may determine which late effects you might experience.

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 osteosarcoma.

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.
• WHO Classification of Tumours. Soft Tissue and Bone Tumours. 5th Edition, Volume 3.

Clinical/ Biomedical Journal Articles

Osteosarcoma (General)

• 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. Available to download here.
• Brandal P, Bjerkehagen B, Bruland OS, Skjeldal S, Bogsrud TV, Hall KS. Synchronous and metachronous skeletal osteosarcomas: the Norwegian Radium Hospital experience. Acta Oncol. 2009; 48(8): 1165-72.
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Epidemiology. Accessed December 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Classification of bone tumours. Accessed December 2009 here.
• Eyre R, Feltbower RG, Mubwandarikwa E, Jenkinson HC, Parkes S, Birch JM, Eden TOB, James PW, McKinney PA, Pearce MS, McNally RJQ. Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981–2002. Br J Cancer. 2009;100, 188-193.
• Gibbs CP, Weber K, Scarborough MT. Malignant Bone Tumors. J Bone & Joint Sur (American). 2001; 83: 1728-1745.
• Kallel R, Ayadi L, Toumi N, Daoud E, Khabir A, Ellouze Z, Charfi S, Makni S, Boudawara TS. Small cell osteosarcoma: a case report. Pathologica. 2009;01(2): 101-4.
• Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006; 125(4): 555-81. Free full text available here.
• Kunze B, Bürkle S, Kluba T. Multifocal osteosarcoma in childhood. Chir Organi Mov. 2009; 93(1): 27-31.
• Lee JA, Kim MS, Koh JS, Kim MS, Kim DH, Lim JS, Kong CB, Song WS, Cho WH, Lee SY, Jeon DG. Osteosarcoma of the Flat Bone. Jpn J Clin Oncol. 2009 Nov 5. [Epub ahead of print]. PMID: 19892781.
• Raymond AK, Ayala AG, Knuutila S. Conventional osteosarcoma. In WHO Classification of Tumours: Pathology and Genetics of Tumours of Soft Tissue and Bone, Kleihues P, Sobin L, Fletcher C et al, eds. Lyon, France: IARC Press; 2002, pp. 264-270. Available free here.
• Samardziski M, Zafiroski G, Tolevska C, Konstadinova-Kunovska S, Vasilevska V. Parosteal osteosarcoma. Bratisl Lek Listy. 2009; 110(4): 240-4. Free full text available here.
• Staals EL, Bacchini P, Bertoni F. High-grade surface osteosarcoma: a review of 25 cases from the Rizzoli Institute. Cancer. 2008; 112(7): 1592-9. Free full text available here.
• Weiss A, Khoury JD, Hoffer FA, Wu J, Billups CA, Heck RK, Quintana J, Poe D, Rao BN, Daw NC. Telangiectatic osteosarcoma: the St. Jude Children's Research Hospital's experience. Cancer. 2007; 109(8): 1627-37. Free full text available here.

Biology of osteosarcoma

• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006; 125(4): 555-81. Free full text available here.
• Lee JA, Kim MS, Koh JS, Kim MS, Kim DH, Lim JS, Kong CB, Song WS, Cho WH, Lee SY, Jeon DG. Osteosarcoma of the Flat Bone. Jpn J Clin Oncol. 2009 Nov 5. [Epub ahead of print]. PMID: 19892781.
• Wang L. Biology of Osteogenic Sarcoma. Pediatric Cancer. The Cancer Journal. 2005; 11(4): 294-305.

Causes and risk factors

• Berman SD, Yuan TL, Miller ES, Lee EY, Caron A, Lees JA. The retinoblastoma protein tumor suppressor is important for appropriate osteoblast differentiation and bone development. Mol Cancer Res. 2008; 6(9): 1440-51.
• Berman SD, Calo E, Landman AS, Danielian PS, Miller ES, West JC, Fonhoue BD, Caron A, Bronson R, Bouxsein ML, Mukherjee S, Lees JA. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A. 2008; 105(33): 11851-6.
• 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. Available at http://www.cure4kids.org/private/courses_documents/m_148/SIOP-2005-Education-Book.pdf
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 from: http://sarcomahelp.org/osteosarcoma.html
• Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008; 134(3): 281-97.
• Deyrup AT, Montag AG, Inwards CY, Xu Z, Swee RG, Unni KK. Sarcomas Arising in Paget Disease of Bone: A Clinicopathologic Analysis of 70 Cases. Arch Pathol Lab Med. 2007; 131(6): 942–946.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Cause. Accessed December 2009 from: http://www.ctu.mrc.ac.uk/euramos/about_o_causes.asp
• Fraumeni J F Jr. Stature and malignant tumors of bone in childhood and adolescence. Cancer. 1967; 20: 967–73.
• Gelberg KH, Fitzgerald EF, Hwang S, Dubrow R. Growth and development and other risk factors for osteosarcoma in children and young adults. Int J Epidemiol. 1997; 26(2): 272-8.
• Gokgoz N, Wunder JS, Mousses S, Eskandarian S, Bell RS, Andrulis IL. Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma. Cancer. 2001; 92(8): 2181-9.
• Huvos AG, Higinbotham NL, Miller TR. Bone sarcomas arising in fibrous dysplasia. J Bone Joint Surg Am. 1972 Jul ;54 (5):1047-56.
• Jaffe HL: Paget's disease of bone. Arch Pathol. 1933; 15, 83-131.
• Kansara M, Thomas DM. Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 2007; 26(1): 1-18.
• Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome. Orphanet J Rare Dis. 2010 Jan 29; 5(1): 2. [Epub ahead of print]
• Lin PP, Pandey MK, Jin F, Raymond AK, Akiyama H, Lozano G. Targeted mutation of p53 and Rb in mesenchymal cells of the limb bud produces sarcomas in mice. Carcinogenesis. 2009; 30(10): 1789-95.
• Longhi A, Pasini A, Cicognani A, Baronio F, Pellacani A, Baldini N, Bacci G. Height as a risk factor for osteosarcoma. J Pediatr Hematol Oncol. 2005; 27(6): 314-8.
• Malkin D. p53 and the Li-Fraumeni syndrome. Cancer Genet Cytogenet. 1993; 66(2): 83-92.
• Paget J., On a form of chronic inflammation of bones (osteitis deformans), Trans Med-Chir Soc, 1877; 60:37:63.
• Ru G, Terracini B, Glickman LT. Host related risk factors for canine osteosarcoma. Vet J. 1998; 156(1): 31-9.
• Scranton PE Jr, DeCicco FA, Totten RS, Yunis EJ. Prognostic factors in osteosarcoma. A review of 20 year's experience at the University of Pittsburgh Health Center Hospitals. Cancer. 1975; 36(6): 2179-91.
• Troisi R, Masters MN, Joshipura K, Douglass C, Cole BF, Hoover RN and the National Osteosarcoma Etiology Group. Perinatal factors, growth and development, and osteosarcoma risk. Br J Cancer, 2006; 95: 1603–1607
• Urfer SR, Gaillard C, Steiger A. Lifespan and disease predispositions in the Irish Wolfhound: a review. Vet Q. 2007; 29(3): 102-11.
• Wang L. Biology of osteogenic sarcoma. The Cancer Journal, 2005; 11(4): 294-305.

Presentation (clinical signs and symptoms)

• 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. Available here.
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Presentation. Accessed December 2009 here.
• Widhe B, Widhe T. Initial Symptoms and Clinical Features in Osteosarcoma and Ewing Sarcoma. J Bone & Joint Sur. 2000; 82: 667.
• Yang JY, Cheng FW, Wong KC, Lee V, Leung WK, Shing MM, Kumta SM, Li CK. Initial presentation and management of osteosarcoma, and its impact on disease outcome. Hong Kong Med J. 2009; 15(6): 434-9.

Diagnosis

• 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. Available here.
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Diagnosis. Accessed December 2009 here.
• National Institute for Health and Clinical Excellence (NICE). Guidance on Cancer Services; Improving Outcomes for People with Sarcoma. The Manual, (March 2006). Available here.
• National Institute for Health and Clinical Excellence (NICE) guidance on cancer services: Improving outcomes in children and young people with Cancer (August 2005) and Improving outcomes for people with sarcoma (March 2006)
• National Institute for Health and Clinical Excellence (NICE). Referral guidelines for suspected cancer. (June 2005). Available here.

Treatment

• Barr RD, Wunder JS 'Bone and soft tissue sarcomas are often curable - but at what cost?' Cancer. 2009; 115(18): 4046-4054.
• 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. Available here.
• Blunt M. Chemotherapy, Cakes and Cancer (An A to Z survival guide for living with childhood cancer). Published by CLIC Sargent, www.clicsargent.org.uk.
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• Cho Y, Kim JD, Chung SH. Osteosarcoma of the patella: biologic reconstruction with allograft. Orthopedics. 2009; 32(10). [e-pub Oct 10], doi: 10.3928/01477447-20090818-27.
• Chou AJ, Kleinerman ES, Krailo MD, Chen Z, Betcher DL, Healey JH, Conrad EU 3rd, Nieder ML, Weiner MA, Wells RJ, Womer RB, Meyers PA; Children's Oncology Group. Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. Cancer. 2009; 115(22): 5339-48.
• DiCaprio MR, Friedlaender GE. Malignant Bone Tumors: Limb Sparing Versus Amputation J Am Acad Orthop Surg. 2003; 11(1): 25-37.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Treatment. Accessed December 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). EURAMOS-1 clinical trial. Accessed December 2009 here.
• Elsevier Guide to Oncology Drugs & Regimens (2008 edition) Drugs and Regimens: High-dose methotrexate, bleomycin, cyclophosphamide, dactinomycin, doxorubicin, cisplatin (Bone). Accessed November 2009 here.
• Ferrari S, Palmerini E. Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma. Curr Opin Oncol. 2007; 19(4): 341-6.
• Heare T, Hensley MA, Dell'Orfano S. Bone tumors: osteosarcoma and Ewing's sarcoma. Curr Opin Pediatr. 2009; 21(3): 365-72.
• Hinds PS, Gattuso JS, Billups CA, West NK, Wu J, Rivera C, Quintana J, Villarroel M, Daw NC. Aggressive treatment of non-metastatic osteosarcoma improves health-related quality of life in children and adolescents. Eur J Cancer. 2009; 45(11): 2007-14.
• Hughes DP. Strategies for the targeted delivery of therapeutics for osteosarcoma. Expert Opin Drug Deliv. 2009 Dec;6(12):1311-21.
• Hughes DP. Novel agents in development for pediatric sarcomas. Curr Opin Oncol. 2009; 21(4): 332-7.
• Janeway KA, Grier HE. Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects. Lancet Oncol. 2010 Jul;11(7):670-678. Epub 2010 Mar 27.
• Kawasoe Y, Yokouchi M, Ueno Y, Iwaya H, Yoshida H, Komiya S. Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma. Oncol Rep. 2009; 22(5): 1045-50.
• Langer T, Stöhr W, Bielack S, Paulussen M, Treuner J, Beck JD; German Late Effects Working Group in the German Society of Pediatric Oncology and Hematology. Late effects surveillance system for sarcoma patients. Pediatr Blood Cancer. 2004; 42(4): 373-9.
• Marulanda GA, Henderson ER, Johnson DA, Letson GD, Cheong D. Orthopedic surgery options for the treatment of primary osteosarcoma. Cancer Contr. 2008; 15(1): 13-20. Free full text available here.
• Meyers PA. Muramyl tripeptide (mifamurtide) for the treatment of osteosarcoma. Expert Rev Anticancer Ther. 2009; 9(8): 1035-49.
• National Institute for Health and Clinical Excellence (NICE). Guidance on Cancer Services; Improving Outcomes for People with Sarcoma. The Manual, (March 2006). Available here.
• NHS England. Proton Beam Therapy. 2020. Find it here.
• Nicholson S, Mulvihill JJ, Byrne J. Late effects of therapy in adult survivors of osteosarcoma and Ewing's sarcoma. Med Pediatr oncol, 2006; 20(1): 6-12.
• O'Day K, Gorlick R. Novel Therapeutic Agents for Osteosarcoma. Expert Rev Anticancer Ther. 2009; 9(4): 511-523.
• Picci P, Mercuri M, Ferrari S, Alberghini M, Briccoli A, Ferrari C, Pignotti E, Bacci G. Survival in high-grade osteosarcoma: improvement over 21 years at a single institution. Ann Oncol. 2009 Nov 4. [Epub ahead of print]. PMID: 19889609.
• Sciubba DM, Okuno SH, Dekutoski MB, Gokaslan ZL. Ewing and osteogenic sarcoma: evidence for multidisciplinary management. Spine (Phila Pa 1976). 2009; 34(22 Suppl): S58-68.
• Siegel HJ, Pressey JG. Current Concepts on the Surgical and Medical Management of Osteosarcoma. Expert Rev Anticancer Ther. 2008; 8(8): 1257-1269.
• Stohr W, Langer T, Kremers A, Bielack S, Lamprecht-Dinnesen A, Frey E, Beck JD; German Late Effects Working Group in the German Society of Pediatric Oncology and Hematology. Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system. Cancer Invest. 2005; 23(3): 201-7.
• Su AW, Chen WM, Chen CF, Chen TH. Innovative trident fixation technique for allograft knee arthrodesis for high-grade osteosarcoma around the knee. Jpn J Clin Oncol. 2009; 39(11): 739-44.
• Whelan J, Patterson D, Perisoglou M, Bielack S, Marina N, Smeland S, Bernstein M. The role of interferons in the treatment of osteosarcoma. Pediatr Blood Cancer. 2009 Nov 9. [Epub ahead of print]. PMID: 19902521
• Winkelmann WW. Rotationplasty. Orthop Clin North Am. 1996; 27(3): 503-23.

Prognosis and prognostic factors

• Buddingh EP, Anninga JK, Versteegh MI, Taminiau AH, Egeler RM, van Rijswijk CS, Hogendoorn PC, Lankester AC, Gelderblom H. Prognostic factors in pulmonary metastasized high-grade osteosarcoma. Pediatr Blood Cancer. 2010; 54(2): 216-21.
• Buecker PJ, Gebhardt M, Weber K. Osteosarcoma. An ESUN Article. Liddy Schriver Sarcoma Initiative, 2005. Accessed December, 2009 here.
• European and American Osteosarcoma Study Group (EURAMOS). Osteosarcoma; Diagnosis. Accessed December 2009 here.
• Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002; 20(3): 776-90. Free full text available here.
• Harting MT, Lally KP, Andrassy RJ, Vaporciyan AA, Cox CS Jr, Hayes-Jordan A, Blakely ML. Age as a prognostic factor for patients with osteosarcoma: an analysis of 438 patients. J Cancer Res Clin Oncol. 2009 Sep 27. [Epub ahead of print] PMID: 19784847.
• Kim MS, Lee SY, Cho WH, et al. Initial tumor size predicts histologic response and survival in localized osteosarcoma patients. J Surg Oncol. 2008; 97(5): 456-61.