Osteosarcoma, a rare cancer of young people

Osteosarcoma, a rare cancer of young people

Osteosarcoma is a rare bone cancer that mainly affects adolescents and young adults. The causes of this tumor, the most common malignant bone tumor, remain poorly understood. Dr Nathalie Gaspar, pediatric oncologist and head of the SPIAJA program (Interdisciplinary Care for Adolescents and Young Adults) at the Gustave Roussy Institute (Villejuif), discusses the symptoms of osteosarcoma, its diagnosis and its treatment.

What is osteosarcoma?

Osteosarcoma is a malignant primary bone tumor, in other words a cancer of them which is characterized by the production of immature bone or osteoid tissue (similar to bone tissue) by tumor cells. This skeletal cancer mainly appears in the long bones, therefore the bones of the limbs (arms and legs). “Osteosarcoma most often develops near the knee and away from the elbow”specifies Dr Nathalie Gaspar.

Half of osteosarcomas develop in the femur and 80% around the knee, either on the lower end of the femur or on the upper end of the tibia. But other sites are possible such as hipsTHE shoulders or even the jaw.

How many people suffer from osteosarcoma in Europe?

Osteosarcoma is a rare malignant tumor, which represents 0.2% of all malignant tumors. In Europe, between 100 and 150 new cases of osteosarcoma are recorded each year, which corresponds to an incidence of 3 cases per million inhabitants.

Who can be affected by osteosarcoma?

This malignant skeletal tumor mainly affects adolescents and young adults. More rarely, it can develop in children under 10 years old. Boys are more often affected than girls (1.4 boys affected for 1 girl).

There is also a peak in the elderly (≥ 60 years), but in their case, osteosarcoma is generally secondary to Paget’s disease, bone infarctions (osteonecroses occurring in the metaphyses and diaphyses of long bones, editor’s note) or to high-dose radiotherapy to bony areas as part of the treatment of another cancer several years previously.

What are the causes of osteosarcoma?

“Osteosarcoma is distinguished from pediatric cancers which affect toddlers and which are linked to embryonic remains, but also from adult cancers which develop much more slowly. The age at which this bone cancer occurs, most often at the peak puberty, as well as its location, at the level of the metaphysis of the long bones, leads us to believe that there is probably a link with growth, but we do not know the exact cause of this tumor.says Dr. Gaspar.

Genetic causes identified

This cancer could be linked to genetic risk factors present in the bone. “ It could result from abnormalities in DNA repair genes or cell cycle genes “. Two major genetic predisposition factors have been identified: Li-Fraumeni syndrome and hereditary retinoblastoma. “It is estimated that 10% of patients with osteosarcoma have a genetic predisposition syndrome; and this proportion rises to 25% when osteosarcoma appears before the age of 10″underlines the pediatric oncologist.

No environmental cause

On the other hand, no environmental cause likely to favor the development of osteosarcoma has been identified to date.

What are the symptoms of a bone tumor?

Pain, first symptom of bone cancer

The main symptom of osteosarcoma is pain. “Osteosarcoma causes bone pain persistent, which worsen over time; fluctuating during the day, they end up waking up at night, undoubtedly due to the inflammatory nature of the tumor.warns Dr. Gaspar.

Localized swelling, a characteristic symptom

Furthermore, continues the specialist, “this skeletal cancer is characterized by the development of a painful, hard lumpwhich grows on the bone. Swelling is in fact a characteristic symptom of osteosarcoma.

Pathological fractures

Finally, the weakening of the bone can lead to so-called pathological fracturesoccurring following a slight trauma or, sometimes, spontaneously.

How to make the diagnosis of osteosarcoma?

What are the tests to detect bone cancer?

The diagnostic process for osteosarcoma involves a consultation with your doctor who will prescribe either an X-ray or a CT scan depending on the location of the suspicious lump and the pain. Depending on the results, an MRI will need to be performed in an expert center.

A tumor biopsy

A biopsy, in other words a sample for analysis of a sample of the suspicious mass, must be done by an expert sarcoma surgeon (belonging to the NETSARC+ network) or more rarely by an interventional radiologist within a center expert ; in this case, the radiologist and surgeon must ensure before the biopsy that the path of the needle will not interfere with subsequent surgery. This collection is done under general or sometimes local anesthesia, depending on the age of the patient, the location of their tumor and the technique.

Looking for metastases

Finally, the search for lung metastases requires a chest scan (computed tomography, CT), while a bone scan or a PET scan will detect bone metastases.

How to treat bone sarcoma?

The general treatment plan for osteosarcoma includes three stages: induction chemotherapy or neoadjuvant chemotherapyand local treatment of the tumor then post-operative chemotherapy or adjuvant chemotherapy. The success of the treatment depends on three factors: the location of the tumor, the presence of metastases at diagnosis and the response to induction chemotherapy. “In the case of localized osteosarcoma with a good response to neoadjuvant chemotherapy, the recurrence-free survival rate is approximately 80% at 3-5 years. In the event of immediate pulmonary metastases or in the event of a poor histological response to chemotherapy, it drops to 50%, and to less than 30% if the risk factors for recurrence accumulate.reports Dr. Gaspar.

Neoadjuvant chemotherapy

It aims to slow down the growth of the bone tumor to facilitate its local treatment, explains the pediatric oncologist. This treatment also serves to prevent the development of metastases or to treat them if they were already there at diagnosis – which is the case in 25 to 30% of patients. 85 to 90% of these metastases are located in the lungs; the rest of the time, they are located on other bones.

The treatment lasts 3 to 4 months. “At the end of this treatment, the response of the tumor to chemotherapy will be evaluated by examining the tumor after the operation. This analysis makes it possible to determine the histological response which is considered good if less than 10% of living tumor cells remain. Histological response is one of the most important prognostic factors in children and young people with non-metastatic osteosarcoma. »

Conservative surgery, sometimes amputation

Surgery represents the key element in the care of people with osteosarcoma. It aims to remove the entire portion of diseased bone then to reconstruct it at the same operating time: we speak of resection/reconstruction. In most cases it is a conservative surgery, that is to say without amputation. “In less than 10% of cases, amputation may nevertheless be necessary when the local invasion is such that it is impossible to preserve healthy tissue at the periphery of the lesion, in particular the vessels.we can read on the IGR website.

Adjuvant chemotherapy

The surgical procedure must be followed by a second so-called adjuvant chemotherapy. Its objective is to prevent the risk of recurrence. Among the risk factors, the existence of metastases at diagnosis, the non-operability of the tumor and the poor histological response to neoadjuvant chemotherapy. In the absence of risk factors, the medications used will be the same before and after surgery; otherwise, other molecules will be used.

Administered intravenously, chemotherapy is relatively toxic: hair loss, nausea, vomiting, mucositis, diarrhea, etc. Combined, these side effects very often result in weight loss. In some more severe cases, chemotherapy can induce bone marrow suppression, resulting in the need to transfuse the patient and administer intravenous antibiotics if they have a fever.

Follow-up or maintenance treatment

Treatment for osteosarcoma stops at the end of post-operative chemotherapy. “There is currently no evidence of the benefit of maintenance treatment, but studies are underway on certain treatments, underlines Dr Gaspar. In total, the treatment of osteosarcoma lasts between 9 and 12 months, which is not without impact on the education of a middle school, high school or student.

Ineffective immunotherapy in osteosarcoma

The objective of immunotherapy is to stimulate the body’s natural immune defenses to fight against the development of cancer cells. “Conventional anti-PD1 and anti-PDL1 immunotherapy drugs are not used to treat osteosarcoma because they do not work alone. This is explained by the fact that sarcomas are tumors poorly infiltrated by lymphocytes and…