Is Ewing sarcoma inherited, and are our other children at risk?

Nothing a child or a parent did caused it. In most children the genetic change that drives the tumour is found only in the tumour cells. Around one in ten patients, however, carries an inherited gene change that raises cancer risk generally, which is why the treating team may suggest genetic counselling for the family. Whether that applies to you is a question for your child's oncologist.

Why does chemotherapy come before the operation?

Because Ewing sarcoma has to be assumed to have sent cells into the bloodstream by the time it is found, even when no scan shows them. Chemotherapy from the start treats the whole body while the tumour is still in place. By the time the operation comes, usually after about twelve weeks, the tumour is usually smaller and the margin around it is easier to plan, and the pathologist can see how much of it the chemotherapy killed.

How long does the whole treatment take?

Most of a year. Chemotherapy runs in cycles every two weeks for about nine months in total, with the operation, radiotherapy or both placed around the twelve-week mark. There are hospital admissions for each cycle and, in between, time at home. The team will give you the planned calendar early, and it will change along the way.

What are the chances of cure?

These are figures for groups of patients and not a prediction for any one child, but parents want to know them. Where the cancer has not spread at diagnosis, around 70 to 80% of children are alive and well five years later with current treatment, and the ten-year results of the trial that set the current chemotherapy schedule showed 76% overall survival. Where it has spread, the figure is around 30%, better when the spread is to the lungs alone than to other bones. Your child's oncologist will talk you through what the scans mean for your child specifically.

Why will there be so many scans after treatment finishes?

Because the cancer can return, most often in the first few years, and because treatment itself has effects that appear later. Follow-up checks the lungs and the bone that was treated, and keeps an eye on the heart, the kidneys and growth. Survivors treated decades ago still carry higher risks of other health problems in adulthood, which is the reason follow-up is lifelong and planned rather than something to be relieved to escape.

Where are children treated?

Children and adolescents with Ewing sarcoma in New South Wales are treated through the children's cancer centres of the Sydney Children's Hospitals Network, with the surgery planned jointly with the sarcoma unit. Chemotherapy and the many admissions it involves happen at the children's hospital; the surgery and radiotherapy are planned by the combined team so that they fall at the right point in the chemotherapy.

Should we look at a clinical trial?

Yes, ask. Nearly everything that has improved the outlook for this cancer, including the two-weekly chemotherapy schedule now used everywhere, came out of children being treated within trials. Being in a trial does not mean receiving an experimental treatment instead of the standard one; it usually means the standard treatment with careful extra follow-up, and sometimes a question added to it.

Ewing sarcoma · Dr Matthew Broadhead

Q: Did we miss it? Should we have brought our child in sooner?

Almost every parent asks this, and the evidence gives a clear answer. Ewing sarcoma takes longer to diagnose than almost any other childhood cancer, because its early symptoms are so ordinary, and in a study of 436 children and adolescents the median time from first symptom to diagnosis was 70 days, longer still in teenagers. That same study found that the time to diagnosis made no difference to whether the cancer had spread or to survival. The delay is part of the disease, not a failure on anyone's part.

Q: Will my child lose the leg or arm?

Usually not. Most Ewing sarcomas of the limbs are removed with the limb preserved, and the missing bone is rebuilt with an implant or with bone graft. In a child who is still growing the implant may be one that can be lengthened in stages. Amputation is now reserved for the small number of tumours that cannot be removed safely any other way, and if it is ever being considered you will be told exactly why.

For parents, first

If you are reading this, your child or a young person you love has probably just been given this diagnosis, and you have been handed a great deal of information at the worst possible moment. This page is written to be read slowly, more than once, and to make the conversations with your child’s team easier to follow. It will not tell you what will happen to your child. It will tell you what the disease is, why treatment is arranged the way it is, and what the evidence says, so that the questions you ask are the right ones.

The essentials

Ewing sarcoma is a cancer that usually starts in bone, most often in children, teenagers and young adults. It is the second most common bone cancer in that age group, after osteosarcoma. It is rare.
It is driven by a single genetic change in the tumour cells. In about 85% of cases two genes called EWSR1 and FLI1 have fused together. Nothing a child or a parent did caused it.
Its early symptoms are ordinary ones, so it is slow to be diagnosed, and that delay has not been shown to affect the outcome. The median time from first symptom to diagnosis is around ten weeks.
Chemotherapy comes first, and runs for most of a year. It is given every two weeks because a randomised trial showed that schedule cures more children than the older three-weekly one, with no extra toxicity.
Surgery, radiotherapy or both deal with the tumour where it started, around the twelve-week mark. Surgery is preferred where it can be done safely; radiotherapy is the alternative, or an addition, where it cannot.
Most limbs are preserved. The missing bone is rebuilt, and in a growing child the reconstruction is planned to grow too.
With current treatment, around 70 to 80% of children whose cancer has not spread are cured. Where it has spread, the figure is around 30%. These are figures for groups, not predictions for your child.
Follow-up is lifelong, by design. The cancer can return, and the treatment has effects that appear years later. Both are watched for.

What Ewing sarcoma is

Ewing sarcoma is a cancer of small round cells that most often arises inside a bone, and sometimes in the soft tissues next to one. It can start in almost any bone, with the pelvis, the thigh bone, the shin bone, the upper arm and the ribs among the commonest sites. It is a disease mainly of the second decade of life, though it occurs in younger children and in adults too.

Under the microscope the cells are small, round and blue, and look like several other cancers of childhood. What makes the diagnosis certain is a genetic test on the biopsy. In about 85% of cases a piece of one chromosome has swapped places with a piece of another, fusing a gene called EWSR1 to a gene called FLI1. The fused gene produces an abnormal protein that reprograms the cell. Beyond that single change, Ewing sarcoma cells carry remarkably few other mutations, which is part of why it is so uniform a disease and why the same treatment works across ages and sites.

That change happened in the tumour, after your child was born. It is not something your child did, or ate, or injured, and it is not something a parent passed on in the ordinary sense. One honest qualification: about one in ten patients with Ewing sarcoma turns out to carry an inherited gene change that raises the risk of cancer generally, which is why some families are offered genetic counselling. Your child’s oncologist will say whether that is relevant to you.

How it shows itself, and why it takes time to find

Pain is the usual first symptom, often worse at night, often in a child who plays sport and has every reason to have a sore leg. Swelling may follow. Some children run fevers or feel unwell. None of this is specific, and a sore limb in an active teenager is nearly always a sore limb.

This is why Ewing sarcoma has one of the longest times to diagnosis of any childhood cancer. In a French study of 436 children and adolescents, the median time from first symptom to diagnosis was 70 days, and it was longer in teenagers and for tumours in the pelvis or the ends of the limbs. The same study looked hard for consequences of that delay and found none: the time to diagnosis was not associated with whether the cancer had spread, with the type of operation needed, or with survival. Parents very commonly blame themselves for not acting sooner. The evidence says the delay is a property of the disease, not of the parents.

Getting the diagnosis

The sequence is an X-ray, an MRI of the whole bone, and then a biopsy, a sample of the tumour taken with a needle under imaging guidance. The biopsy is planned by the team that will do the operation, because the needle track has to be removed with the tumour later. This is the reason a suspected bone tumour is referred to a sarcoma centre before anything is sampled, and it is covered in more detail on the tests and diagnosis page.

Once the diagnosis is confirmed, scans look for spread: a CT scan of the chest, a whole-body scan (a PET scan or a bone scan), and in some centres a sample of bone marrow. These tests decide whether the cancer is localised, found only where it started, or metastatic, present elsewhere as well, and that distinction shapes everything that follows.

Why chemotherapy comes first

Ewing sarcoma is treated on the assumption that cells have already left the bone and are travelling, too few to see on any scan. Chemotherapy therefore starts straight away, while the tumour is still in place, and treats the whole body. The operation or radiotherapy comes later, when the tumour has usually shrunk and the pathologist can measure how well the drugs worked on it.

The drugs are a combination used for decades: vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide, given over about 14 cycles. What changed in recent years is the timing. The Children’s Oncology Group ran a randomised trial of 568 children and young adults with localised Ewing sarcoma, giving the same drugs either every three weeks or every two weeks. Five years on, 73% of those treated two-weekly were alive without the cancer returning, against 65% on the three-weekly schedule, and the side effects were no worse. At ten years the advantage held: 70% against 61% event-free, 76% against 69% overall survival, with no increase in second cancers. Two-weekly treatment is now the standard, and in 2022 a European trial of 640 patients confirmed that this American-style regimen was better than the regimen Europe had been using, so it is the approach used internationally.

The practical shape of this is nine months or so of hospital admissions every fortnight, with a growth-factor injection in between to help the blood counts recover. Hair falls out. There will be admissions with fever. The team will prepare you for all of it, and the chemotherapy and radiotherapy page covers the general ground.

The operation, and when radiotherapy is used instead

Around week 12 or 13, after the first six cycles, attention turns to the tumour itself. There are two ways to deal with it, and the choice depends on where it is.

Surgery removes the affected segment of bone with a cuff of healthy tissue around it, and rebuilds what was taken. Around the knee or the hip that usually means an implant that replaces the bone and the joint; elsewhere it may mean bone graft. In a child who is still growing the implant may be one that can be lengthened in stages as the other limb grows, which brings its own planned sequence of procedures over the following years. All of this is discussed with you before the first operation. The surgery page describes what the admission and recovery are like.

Radiotherapy is used where the tumour cannot be removed safely, which is often the case in the pelvis and the spine, or in addition to surgery where the margin is close or the tumour responded poorly to chemotherapy. In a Children’s Oncology Group analysis of 465 children with localised Ewing sarcoma of bone, those treated with radiotherapy alone had about two and a half times the risk of the tumour returning where it started compared with surgery, but no difference in survival once other factors were accounted for. The authors’ conclusion is the one most teams follow: operate when it can be done well, and use radiotherapy where it cannot. In the pelvis, the hardest site, combining surgery with radiotherapy gave a local recurrence rate of 6% against 25% with radiotherapy alone.

Chemotherapy resumes after the local treatment and continues to complete the course.

What the outlook is, honestly

Parents ask, and they should have an answer rather than a deflection. The figures below are for groups of patients and are not a prediction for your child, whose team will interpret them in the light of the scans.

Where the cancer has not spread at diagnosis, around 70 to 80% of children are alive and well five years later with current treatment. Where it has spread, the figure is around 30%, and better when the spread is to the lungs alone than when bone is involved. The strongest single factor is whether the cancer had spread when it was found; after that, a tumour in the pelvis or spine, an older age at diagnosis and a larger tumour each carry somewhat more risk. How much of the tumour the chemotherapy has killed, which the pathologist reports after the operation, also matters.

Two things to hold onto. The outlook has improved steadily with each generation of trials, and it continues to. And the chemotherapy schedule your child will receive is the one that produced the best results ever recorded for this disease.

After treatment

Treatment ends, and a different phase begins. The cancer can return, most often in the first two to three years but occasionally much later, so follow-up with scans of the chest and the treated bone continues for years. The treatment also leaves marks that appear with time. Doxorubicin can weaken the heart; ifosfamide can affect the kidneys; radiotherapy to a growing bone affects its growth and carries a small long-term risk of a second cancer in the treated area; and fertility can be affected, which is why preserving it is discussed before chemotherapy begins wherever that is possible.

The long-term studies are sobering and should be read in context. Among adults who had survived Ewing sarcoma in childhood, treated between 1970 and 1986, 85% had at least one chronic health condition 35 years later, and 14% had developed a second cancer. Those were older treatments; the current regimen has not shown higher rates of late effects than its predecessors, apart from a slightly higher rate of kidney problems. The point for a parent is not alarm but design: because these risks are known, follow-up is lifelong and organised around them, with the heart, the kidneys, growth and the treated bone each checked in turn. The after treatment page describes what that looks like.

Where children are treated, and who to lean on

In New South Wales, children and adolescents with Ewing sarcoma are treated through the children’s cancer centres of the Sydney Children’s Hospitals Network, and the surgery is planned jointly with the sarcoma unit so that it falls at the right point in the chemotherapy. You will meet a great many people: oncologists, surgeons, radiation oncologists, pathologists, nurses, physiotherapists, social workers and teachers. It is normal to lose track of who is who. Ask for one named person to be your point of contact, and use them.

Beyond the hospital, two Australian organisations exist for exactly this situation. Redkite supports families of children with cancer, including with the practical and financial strain. Canteen supports young people aged 12 to 25 who have cancer or whose sibling does, which matters: the brothers and sisters are carrying this too. The Australia and New Zealand Sarcoma Association has information written for Australian families, and the National Cancer Institute’s patient summary is a reliable, regularly updated reference if you want more detail than this page gives. The for family and carers page on this site covers the practical side of appointments and admissions.

What this means for you

Your child has a rare cancer with a long, demanding, well-worked-out treatment, and a real prospect of cure. The order of that treatment, chemotherapy first, the tumour dealt with in the middle, chemotherapy to finish, is not arbitrary: each part has a job, and each has been tested in children against the alternatives. The questions worth asking at the next appointment are whether the cancer has spread, where exactly it is, what the plan is for the tumour itself and when, and who your one point of contact will be. Write the answers down. You will want them again.

Ewing sarcoma