Osteosarcoma - diagnostics and treatment at the cancer center

Therapy methods

Modern treatment of osteosarcoma necessarily involves the following:

• removal of bone tumor;
• removal of discovered metastases;
• polychemotherapy, i.e. using not one drug, but their combination.

Osteosarcoma is a malignant bone tumor most commonly found in children and adolescents (2-3 new cases per 1 million children or adolescents), but can also occur in adults. In adults, not only the tubular bones of the limbs, but also the vertebrae, jaw, and pelvic bones often get damaged. It was noticed that the majority of patients are tall, and the older the patient is, the more likely the process will develop in an atypical place, while the typical localization of osteosarcomas is in the large bones of the limbs near the joints.

The reasons for it have not been completely revealed until now. But despite this, its symptoms are typical and manifest themselves in increasing pains in the affected bone. An early diagnosis is very important for the life prognosis. Osseal sarcomas at a late stage are characterized by rapid progression, and therefore treatment always includes chemotherapy. Accordingly, at the slightest suspicion it is worth visiting a specialized center. Point mutations in genes are considered to be the main cause of this condition. In combination with external irradiation, they can lead to development of bone tumors.

Osteogenic sarcoma, or briefly osteosarcoma, is the same malignant neoplasm as cancer or melanoma, but it is wrong and inappropriate to call it cancer. Cancer develops only from cells of the mucous membrane, and from any other tissue, while sarcoma occurs only in the connective tissue, and osteogenic sarcoma is derived from bone elements.

All of these processes have common features of malignant growth: unrestrained reproduction of cells, aggressiveness towards surrounding tissues, the ability to form metastases, an easy adaptability to serious changes in the body, and they are treated using three methods: surgery, irradiation and antitumor drugs.

Symptoms of osteosarcoma

The first symptoms of osteosarcoma are often associated with injuries, which are not uncommon in childhood. First, pains appear in the limb, which gradually increase. Later, a swelling and mobility restriction in a nearby joint are added. Sometimes osteosarcoma can make its debut with a pathological fracture, i.e. the one not associated with a significant mechanical damage.

At the earliest stage, when the tumor is still inside the bone, the condition does not manifest itself, because its first symptom, pain, occurs only when periosteum (the superficial bone layer) is destroyed, since it is well innervated. The main bone substrate, where the malignant process develops, practically does not contain nerve endings, so for a long time there are no signs of trouble.

On the face, a neoplasm can be detected at an early stage, since the deformation of the jaw in this anatomical zone is more visible, and dental problems are often provoked. This localization is typical for young persons more attentive to their own appearance.

Unlike other tumors, here the general condition is disturbed only in advanced cases (at the last stage), which is the reason for late diagnosis. This is the time when a weakness, a sharp decrease in appetite, weight loss and anemia appear.

Regarding frequency of lesions by anatomical regions, the superiority belongs to the femur in the knee area, then the humerus in the upper third, and lesion of the vertebrae and pelvic bones are also characteristic for adults, as well as of the jaw in the facial skull.

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Sergeev Petr Sergeevich

Head of oncology department, oncologist, surgeon, candidate of medical science

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Bone tissue biopsy

The final diagnosis will be established only by microscopic examination of a tumor tissue piece taken during a biopsy. This is the most complex yet mandatory diagnostic manipulation. Biopsy is performed in different ways, preference is given to techniques that minimally traumatize or promote the dispersion of malignant cells in the surrounding tissues.

The clinic performs biopsy under CT (computed tomography) control. It is an accurate and least traumatic method.

When sarcoma has spread into the surrounding structures, a soft tissue component is taken for the study without a biopsy of the bone itself, which ensures minimal injury and protects against a possible pathological fracture connected with a bone structural integrity violation. A piece of tumor tissue is always preserved «for the future», so that when new genetic markers appear, it would be possible to determine the sensitivity to effective drugs.

Of course, the diagnostic menu includes chest radiography and abdominal ultrasound to identify asymptomatic metastases, as well as blood tests and osteoscintigraphy (isotope skeletal scanning).

Osteosarcoma stages

The treatment tactics and prognosis are determined not only by the tumor size, but also by the degree of its aggressiveness that depends on cell differentiation.

Differentiation involves:

• differences between a sarcoma cell and a normal one, the more there are, the more aggressive is the process;
• cell potency to fission determined by the number of mitoses in a cell, since cells that fission very quickly ensure rapid growth of the entire tumor node;
• presence of necroses, that is, groups of dead cells among the living ones.

Next to the stage from 1 to 4, the degree of cell differentiation is indicated as a letter G with numbers: low-grade differentiation is indicated as G-3 and denotes an increased degree of malignancy; high-grade is encoded as G1, such neoplasms are less aggressive; there is also an intermediate variant, moderate differentiation G-2; complete loss by cells of structural features characteristic of healthy tissue indicates high aggressiveness and is indicated as undifferentiated G-4.

The spreading of sarcoma in the bone is indicated by the letter T and is evaluated in two ways: according to the formation size or extent of damage to the superficial bone layer. Sarcoma not exceeding 8 cm is regarded as T1.

M, the last criterion, indicates the presence or absence of metastases.

In grouping by stages, all criteria are always taken into account: Thus, stage 1 implies the size of a bone tumor no more than 8 cm and only G1 or G2; With the same size and malignity, G3 or G4 will be counted as stage 2. Stage 2 also includes a bone lesion exceeding 8 cm with the same high malignity degree.

Any G of a sarcoma, the dimensions of which cannot be exactly determined, will be graduated as stage 3. The last stage 4 always implies metastases regardless of size and differentiation.

The condition prognosis is more influenced by the aggressiveness of the neoplasm, its spread in the body, the poor response to chemotherapy and the elderly age that imposes restrictions on antitumor treatment due to concomitant chronic diseases.

Radical surgical treatment of osteosarcomas

Surgery is the leading method of treatment leading to complete recovery or long-term remission. The sensitivity of osteoid sarcoma to radiation is not significant, and chemotherapy is considered today a mandatory complement to surgical therapy.

Not long ago, the main methods of radical treatment were crippling surgeries that completely removed the affected anatomical region. Today, the advancement of chemotherapy and the possibility of replacing the affected bone with a functional prosthesis made it possible to prioritize organ-preserving interventions. Crippling operations such as amputation or limb exarticulation currently make up hardly a tenth of all interventions for osteosarcoma.

However, crippling interventions do not have an alternative when prosthetics is technically impossible, or when a sarcoma is disintegrating due to its large size with complications such as bleeding.

Preferable are resections of the bone segment when up to 3-5 cm of normal healthy tissue are removed from all sides, complemented by prosthetics as necessary. Titanium-containing products are recognized as the gold standard for prostheses, and the higher the titanium content, the better. Such endoprostheses do not irritate the surrounding tissues, do not poison the body, are quite durable and do not interfere with subsequent CT and MRI.

The surgery scope is chosen by the case conference and agreed with the patient, the main criteria for the radical operation being the absence of malignant cell dissemination of the tissues that remain, which precludes a rapid recurrence. When planning the intervention, the future functionality of the operated anatomical region, the possible range of motion, is taken into account.

Supplementing of surgical treatment with chemotherapy before and after the intervention has significantly reduced the frequency of relapses. Additional cytostatic therapy is not performed for osteogenic sarcomas of low malignity, when the probability of recurrence is minimal, with small tumors and in the absence of a tumor response to treatment (drug resistance).

Chemotherapy can transfer an inoperable process into a removable type, stops the growth of distant metastases, reduces clinical manifestations of a relapse. The metastatic stage of the disease is an indication for anti-tumor drug exposure.

Study of the removed bone under a microscope allows a detailed assessment of the effect and further treatment planning.

A very good result with death of 90% of the cells is referred to as «grade III-IV drug pathomorphism», and after surgery, 4 more cycles are performed for such patients by the same scheme as before the surgery. With a lesser pathomorphism degree, the combination of chemotherapy drugs is changed, and treatment lasts a whole year.

At the metastatic stage of osteosarcoma, cyclic polychemotherapy is performed, which does not exclude a surgical intervention, since removal of metastases in the lungs affects the patient’s life span.

Formally, slightly less than ten cytostatics are active with osteosarcoma, and their skillful combining against the background of accompanying individual symptomatic therapy, supplemented by timely palliative intervention and optimal removal of metastatic foci, can prolong life for months and years preserving its good quality.

How is chemotherapy performed?

The standard course of treatment is 3-4 cycles before surgery, and after the intervention, everything will be determined by drug pathomorphism, the degree of sarcoma cell deaths. For each level of pathomorphism, the optimal scheme and duration of treatment have been determined in clinical studies, as a rule, not exceeding a year after the surgical stage.

A small number of cytostatic drugs is used, but in high doses and with a long-term infusion from 72 to 96 hours through special devices called infusomats. The interval between courses is no more than three weeks.

Therapy entails toxic reactions, the severity of which can be reduced by special preparation programs offered by the Clinic Medicine 24/7 and by individual nutritional support.

Palliative surgery for osteosarcoma

With relapse and metastases, treatment not limited to chemotherapy, small interventions are also performed that are aimed at removing tumor foci and can significantly improve the prognosis. The methods used include bone re-resection in case of recurrence, and removal of metastases in the lungs or liver, including local destruction by liquid nitrogen or radiofrequency ablation.

In all cases, an attempt is to remove all metastatic foci, be it at once or in turns over several cycles of antitumor chemotherapy, since only in this case the patient can count on a long and comfortable life.

The material was prepared by the oncologist, Head of Oncology Department of the Clinic Medicine 24/7 Petr Sergeevich Sergeev, Candidate of Medical Science.

When the masterly surgical skills of an expert are combined with the wide diagnostic capabilities of the Clinic Medicine 24/7, even with a small range of effective chemotherapy drugs and treatment toxicity more can be achieved than envisaged by standards. The Clinic’s patients can count on an individual approach to the patient and his/her condition, because our interest lies in your recovery.

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