Treatment of astrocytomas of the brain and spinal cord

Brain astrocytoma is a collective name for several variants of the glial tissue tumor process, which are distinguished by their aggressiveness in terms of growth, the probability of degeneration into a malignant tumor, and the prognosis of treatment. It is clear that we can not talk about the general scheme of therapy. At the same time, not only approaches to the treatment of different types of astrocytes differ, but also therapeutic schemes for each individual patient.

There are official specially developed  protocols for the diagnosis and treatment of astrocytomas of one of the glial tumors, and the recommended regimens for the treatment of certain types of tumors, taking into account their degree of malignancy. Abroad, medicine works according to a common proven protocol for treating benign and malignant tumors, which gives good results. In our country, this unity is not observed. Treatment protocols are often compiled by the attending physicians with a focus on their own experience, although in fact they must be developed by specialists to help the practitioner.

In Ukraine, the introduction of treatment protocols that familiarize physicians with effective methods of diagnosing and treating a specific disease (in this case, astrocytomas) and enabling patients to control the validity of the doctor’s actions, is still under development. Few experts use international methods, and domestic ones are often not composed by those people and respond to the wrong questions (to the fore, they raise questions about the cost of treatment, which in no way helps save the patient's life, while the current methods do not receive the necessary attention).

It is clear that even the most highly scientific protocols that offer treatments with proven effectiveness are not a dogma. Medicine does not stand still, developing more and more new methods to save the patient and prolong his life as much as possible, therefore, existing protocols, which are in essence documented clinical guidelines, should be regularly changed to optimize the work of the doctor.

Treatment with unproven effectiveness, based on the knowledge and experience of a particular doctor, is one of the reasons for the poor prognosis of the disease. In oncology, time decides a lot, and the doctor does not have the right to make a mistake, checking various methods of treatment on the patient. Protocols for the treatment of tumors of various malignancies are designed to facilitate the work of a doctor and make it as effective as possible. Nobody forbids the use of new techniques with unproven efficacy with the consent of the patient or his family, but this should be done as ancillary procedures within the treatment protocol.

Since the treatment of tumor diseases includes various types of patient care, the protocol for treating such patients relies on appropriate protocols (for example, protocols for providing palliative care for pain and bleeding to incurable patients), which are used not only in the practice of oncologic hospitals.

Today, astrocytoma treatment protocols include the use of such standard methods as surgery, chemotherapy and radiotherapy, which has nothing to do with radio wave treatment, and is inherently an effect on the lesion with ionizing radiation (radiation therapy). Consider these methods in more detail.

Surgical treatment of astrocytomas

If in the treatment of most somatic diseases where surgical intervention is required, the operation is considered an extreme measure, then in the case of the tumor process, it is preferred in the first place. The fact is that classical surgery among the treatment of tumors is considered the safest for humans, since its effects cannot be compared with the effects of chemotherapy and radiation. However, it is not always possible to remove the tumor surgically, therefore, the decision to conduct the operation is made taking into account such a thing as “operability”.

The need for surgery in astrocytoma of the brain is due to the fact of the presence of a brain tumor, because as the neoplasm grows (any degree of malignancy), the mass effect increases (its effects are compression of cerebral vessels, deformation and displacement of its structures). In determining the possible volume of surgical intervention, the patient’s age, general status (the patient’s Karnofsky condition and the Glasgow scale), the presence of concomitant diseases, the location of the tumor and its surgical accessibility are taken into account. The task of the surgeon is to remove as much as possible all components of the tumor, minimizing the risks of functional complications and death, restore the outflow of fluid (liquor circulation), and clarify the morphological diagnosis. The operation must be carried out in such a way that it does not reduce the patient’s quality of life, but help him live a more or less fulfilling life.

The choice of surgical tactics is based on the following points:

• location and surgical accessibility of the tumor, the possibility of its total removal,
• age, condition of the patient according to Karnovsky, available comorbidities,
• the possibility of reducing the effects of the mass effect using the selected operation,
• interval between operations in case of recurrent tumor.

Options for surgical treatment of brain tumors are: open and stereotactic biopsy, complete or partial resection of the tumor. Removal of brain astrocytoma has various objectives. On the one hand, this is an opportunity to reduce intracranial pressure and the intensity of neurological symptoms by minimizing the volume of the tumor. On the other hand, it is the best option for taking the required amount of biomaterial for histological examination in order to accurately determine the degree of malignancy of the tumor. The tactics of further treatment depends on the latter factor.

If it is impossible to remove the entire neoplasm (astrocytomas, under the total removal, are the removal of a tumor within the visible healthy tissue, but not less than 90% of tumor cells) resort to partial resection. This should help reduce the symptoms of intracranial hypertension, and also provides material for a more complete examination of the tumor. According to studies, the life expectancy of patients after total resection of the tumor is higher than in patients with subtotal resection [1].

Tumor removal is performed using craniotomy, when a hole is made in the soft and bone covers of the head through which surgical removal of the tumor takes place using microsurgical techniques, as well as navigation and control optics. After surgery, the meninges are hermetically sealed with an implant. An open biopsy is performed in the same way.

With stereotactic biopsy, the material for the study is taken using a special needle. Minimally invasive surgery is performed using a stereotactic frame and navigation system (tomograph). The biomaterial is collected by means of a special needle without trepanning of the skull. [2]This method is used in certain cases:

• if the differential diagnosis is difficult (there is no possibility to differentiate a tumor from inflammatory and degenerative foci, metastases of another tumor, etc.),
• if it is not possible to remove the tumor surgically (for example, there are contraindications to surgery) or such removal is considered inappropriate.

For high accuracy of the diagnosis, the site for tissue that intensively accumulates a contrast agent should serve as a material for histological examination.

In elderly patients or those who have severe somatic diseases, even the use of minimally invasive diagnostic techniques may cause concern. In this case, the treatment strategy is based on clinical symptoms and tomogram data.

After removal, astrocytomas of the brain necessarily conduct its histological examination with the definition of the type of tumor and its degree of malignancy. This is necessary to clarify the diagnosis and can affect the tactics of patient management, since the probability of an erroneous diagnosis remains even after a stereotactic, and sometimes an open biopsy, when a small part of the tumor cells is taken for examination. [3]The tumor degeneration process is gradual, therefore, not all of its cells at the initial stage of malignancy can be atypical.

The final and reliable diagnosis is made on the basis of a conclusion about the nature of the tumor by 3 specialist pathologists. If a malignant tumor is detected in a child under 5 years old, an additional genetic test is prescribed (using an immunohistochemical method, a deletion of the INI gene is studied, which can lead to changes in the properties of the cells and their uncontrolled division).

Immunohistochemical analysis of a tumor with an IDH1 antibody is also carried out in the case of glioblastoma. This allows you to make predictions about the treatment of this aggressive form of cancer, which causes the death of brain cells within 1 year (and that provided the treatment is carried out).

Histological examination of tumor tissues allows an irrefutable diagnosis to be made only in case of a sufficient amount of biomaterial. If it is small, no signs of malignancy are found in it, and the focal proliferative activity index (Ki-67 marker) is not more than 8%, the diagnosis may sound twofold - “WHO grade 2 astrocytoma with a grade 3 tendency”, where WHO is the international abbreviation health organizations. [4]  An immunohistochemical analysis of proteins of the Bcl-2, Bcl-X, Mcl-1 family is also carried out [5]. The correlation of ATRX, IDH1 and p53 in glioblastoma with patient survival has been proven.[6]

If we are talking about a malignant astrocytoma without necrotic foci, if a biopsy material is insufficient, a diagnosis of “malignant astrocytoma WHO grade 3-4” can be made. Such a formulation once again confirms the fact that astrocytes are predisposed to progressing and degenerating into a malignant tumor, therefore even neoplasms of grade 1 to 2 of malignancy are better treated without waiting for them to change their properties and behavior.

Modern technologies (radiosurgery)

Small tumors in the early stages of the disease, according to indications, can be removed using low-impact techniques. These include methods of stereotactic radiosurgery, which remove benign and malignant neoplasms without tissue incisions and craniotomy with the help of ionizing radiation.

Today, neurosurgeons and neuro-oncologists use 2 effective systems: cyber-knife based on photon irradiation and gamma-knife using gamma radiation. The latter is used only for intracranial operations. Through a cyber-knife, it is possible to remove tumors of various localization without rigid traumatic fixation (when using a gamma knife, the patient's head is fixed with a metal frame screwed into the skull, a thermoplastic mask is sufficient for a cyber-knife), pain and anesthesia.[7], [8], [9], [10]

Brain astrocytoma can be found both in the head and in the spinal cord. With the help of a cyber-knife, it is possible to remove such tumors without traumatic intervention on the spine.

When astrocytomas remove the brain, the main requirements are:

• tumor verification, i.e. Evaluation of the morphological nature of the neoplasm, diagnosis clarification by biopsy,
• tumor size is not more than 3 cm in diameter,
• the absence of serious diseases of the heart and blood vessels (mandatory ECG),
• the patient's status on the Karnofsky scale is not lower than 60%,
• patient's consent to the use of radiation therapy (it is used in radiosurgical systems).

It is clear that it is inappropriate to treat this disease by this method. It makes no sense to locally irradiate a huge tumor without surgical removal, since there is no conviction that all pathological cells will die. The effectiveness of radiosurgery in the treatment of diffuse tumors with diffuse localization is doubtful, because ionizing radiation causes the death of not only cancer cells, but also healthy brain cells, which, with a large tumor size, can make a person disabled in all senses of the word.

The lack of radiosurgery can be considered the impossibility of verification of the tumor after its removal, since there is no biological material for histological examination.

Astrocytoma Radiation Therapy

The use of radiosurgical technologies for the treatment of benign and well-differentiated malignant astrocytomas at an early stage of their development gives an exhaustive answer to the question of whether astrocytomas are irradiated. Radiation therapy can not only slow down the growth of a tumor, it causes the death of cancer cells.

Usually, radiological therapy is used in the case of malignant neoplasms, benign tumors are sufficiently surgically removed. But the cunning of glial tumors consisting of astrocytes lies in their susceptibility to relapses. In this case, both malignant and benign tumors can recur. Relapse of benign astrocytomas of the brain is often accompanied by the rebirth of a generally safe tumor into a cancer. Therefore, doctors prefer to play it safe and fix the result of the operation with the help of radiotherapy.[11]

Indications for radiotherapy can be either a biopsy-confirmed diagnosis of a benign or malignant tumor, or a relapse of the tumor after treatment (including with the use of radiotherapy). The procedure can also be prescribed if verification of the tumor is impossible (without a biopsy) if astrocytomas are located in the brain stem, at the base of the skull, in the area of the optic chiasm, and in some other areas difficult for surgical intervention.

Since the majority of patients with astrocytomas of the brain are patients of oncological clinics (it so happened that the distribution of malignant and benign glial tumors is not in favor of the latter), the treatment of tumors with radio-surgical methods is less common than remote fractional radiotherapy. In malignant tumors, it is prescribed after the removal of abnormal cells. The interval between the operation and the first radiation therapy session is usually 14-28 days.[12], [13]

In the case of particularly aggressive tumors with lightning growth, radiation therapy in satisfactory condition of the patient can be prescribed after 2-3 days. Irradiation is subjected to the lesion remaining after removal of the tumor (bed) with the capture of 2 cm of healthy tissue around. According to the standard, radiation therapy provides for the appointment of 25-30 fractions within 1-1.5 months.

The irradiation zone is determined by the results of MRI. The total radiation dose of the focus should not be more than 60 Gy, if the spinal cord is irradiated - even less, up to 35 Gy.

One of the complications of radiation therapy is education after a couple of years of necrotic focus in the brain. Dystrophic changes in the brain lead to a violation of its functions, which is accompanied by corresponding symptoms similar to those of the tumor itself. In this case, the patient is examined and differential diagnostics (PET is prescribed with methionine, computer or magnetic resonance spectroscopy) in order to distinguish radiation necrosis from tumor recurrence.[14]

Along with remote radiotherapy, contact radiation therapy (brachytherapy) can also be used, but in the case of brain tumors it is used very rarely. In any case, the flow of ionizing radiation, acting on the pathological DNA of cells and destroying it, leads to the death of tumor cells, which are more sensitive to this effect than healthy cells. Upgraded linear accelerators can reduce the degree of destructive effects on healthy tissue, which is especially important when it comes to the brain.

Radiation therapy helps to destroy the remaining hidden tumor cells and prevents its recurrence, but this treatment is not shown to everyone. If doctors see that the risk of possible complications is high, radiotherapy is not performed.

Contraindications to radiation therapy can be considered:

• location and infiltrative tumor growth in vital parts of the brain (trunk, subcortical nerve centers, hypothalamus).
• cerebral edema with symptoms of dislocation (displacement) of the brain
• the presence of postoperative hematoma,
• purulent-inflammatory areas in the zone of exposure to ionizing radiation,
• inadequate patient behavior, increased psychomotor irritability.

Radiotherapy of incurable patients with serious somatic diseases is not subjected to radiation, which can only worsen the patient's condition and speed up the inevitable end. Palliative therapy is prescribed to such patients (according to the appropriate protocol) in order to reduce pain and prevent severe bleeding. In other words, as far as possible, doctors try to alleviate the suffering of the patient in the last days and months of his life.

Chemotherapy astrocytomas

Chemotherapy is a method of systemic exposure of the body in order to destroy the remaining atypical cells and prevent their re-growth. The use of potent agents, detrimental to the liver and alter the composition of the blood, is justified only in the case of malignant tumors. [15]  Early chemotherapy, parallel chemotherapy and short chemotherapy after radiotherapy are possible and well tolerated [16].

If we are talking about astrocytomas, then in some cases chemotherapy can be given for a benign tumor, if the risk of its transformation into a cancer one is great. For example, in people with a hereditary predisposition (there have been cases of confirmed oncology in the genus), benign neoplasms, even after surgical removal and radiation therapy, can recur and turn into cancerous tumors.

Identical situation can be traced with twofold diagnoses, when there is no certainty that the tumor has exactly a low degree of malignancy or if there are contraindications to radiation therapy. In such cases, the lesser of two evils choose the smallest, i.e. Chemotherapy.

A malignant astrocytoma of the brain is an aggressive tumor, prone to rapid growth, therefore, it is necessary to act against it with the same aggressive methods. Since astrocytomas are referred to as primary brain tumors, drugs are selected for the treatment of this type of oncology, but taking into account the histological type of the tumor.

In chemotherapy, astrocytomas are used cytotoxic anticancer drugs alkylating action. The alkyl groups of these drugs are able to attach to the DNA of atypical cells, destroying it and making it impossible for them to divide (mitosis). Such drugs include: Temodal, Temozolomid, Lomustin, Vincristine (a vinca alkaloid-based drug), Procarbazine, Dibromodulcitol, [17]and others. It is possible to assign:

• platinum preparations (Cisplatin, Carboplatin), which inhibit the synthesis of atypical cells, [18]
• topoisomerase inhibitors ("Etoposide", "Irinotecan"), which prevent cell division and synthesis of hereditary information),
• monoclonal IgG1 antibodies (“Bevacizumab”) that interfere with the blood supply and nutrition of the tumor, impeding its growth and metastasis (they can be used independently, but more often in combination with topomerase inhibitors, for example, with the drug “Irinotecan”). [19]

In anaplastic tumors, nitro derivatives (Lomustin, Fotemustin) or their combinations (Lomustine + other drugs: Procarbazine, Vincristine) are most effective.

When anaplastic astrocytoma relapses, Temozolomide (Temodal) is the drug of choice. It is used in isolation or in combination with radiotherapy, complex treatment is usually prescribed for glioblastomas and recurrent anaplastic astrocytomas.[20]

For the treatment of glioblastoma often used two-component schemes: "Temozolomid" + "Vincristine", "Temozolomid" + "Bevacizumab", "Bevacizumab" + "Irinotecan". A course of treatment is prescribed for 4-6 cycles with intervals of 2-4 weeks. "Temozolomid" is prescribed daily for 5 days, the remaining drugs must be administered on certain days of treatment 1-2 times during the course.

It is believed that such therapy increases the survival rate of patients with malignant tumors during one year by 6%. [21]Without chemotherapy, patients with glioblastoma rarely live for more than 1 year.

To assess the effectiveness of radiation and chemotherapy, re-MRI is performed. During the first 4-8 weeks, an atypical picture may be observed: the contrast increases, which may lead to an assumption about the progression of the tumor process. Do not make hasty conclusions. More relevant 4 weeks after the first MRI, repeat and, if necessary, PET examination.

He defines the criteria by which the efficacy of therapy can be assessed, but at the same time it is necessary to take into account the patient's central nervous system condition and the accompanying corticosteroid treatment. The permissible goal of complex treatment is to increase the number of surviving patients and those who have not experienced signs of disease progression within six months.

In case of a 100% disappearance of a tumor, they indicate a complete regression, a reduction in the neoplasm by 50% or more - a partial regression. Lower rates indicate stabilization of the process, which is also considered a positive criterion for stopping tumor growth. But the increase in the tumor by more than a quarter indicates the progression of cancer, which is a bad prognostic symptom. Symptomatic treatment is also carried out.

Astrocytoma treatment abroad

The state of our medicine is such that people are often afraid of dying not so much from a disease as from a surgical error, the lack of necessary medicines. The life of a person with a brain tumor and so not envy. What are only constant headaches and epilepsy attacks. Patients' minds are often at the limit, therefore not only professional diagnostics and the right approach to treatment are very important, but also the appropriate attitude towards the patient by the medical staff.

In our country people with disabilities and people with serious illnesses are still in an ambiguous position. In words, many feel sorry for them, but in fact they do not receive the love and care they need. After all, pity is not so much help, which stimulates to rise to your feet after an illness. Here we need the support and suggestion of confidence that there is almost always hope and you need to use even the slightest opportunity to live, because life is the highest value on Earth.

Even people with Stage 4 cancer, who are given a cruel sentence, need hope and care. Let a person set aside some couple of months, but you can live them differently. Doctors can alleviate the patient’s suffering, and relatives can do everything so that a loved one can die happy.

Some people, with the support of others, do more in the days and weeks allotted than in all their lives. But for this you need the appropriate attitude. Cancer patients like no one else need the help of psychologists to help change their attitude to the disease. Alas, in domestic medical institutions such help is not always offered.

We have oncologic dispensaries and specialized departments, we treat cancer of different localization, there are qualified specialists for this, but the equipment of our medical centers often leaves much to be desired, not all doctors undertake brain surgery, psychological help and the attitude of the staff usually leaves much to be desired. All this causes the search for the possibility of treatment abroad, because the reviews of foreign clinics are overwhelmingly positive, full of thanks. This gives hope even to those who, it would seem, is doomed due to the diagnosis, which, moreover, may be inaccurate (poor equipment with diagnostic equipment increases the risk of error).

We have become accustomed to the fact that foreign doctors are taken to treat patients who were refused by domestic specialists. So, in the clinics of Israel, many patients with malignant anaplastic form of astrocytoma have been successfully treated. People got the opportunity to live on a full life. At the same time, the statistics of relapse of treatment in Israeli clinics are much lower than in our country.

Today, Israel, with its high-tech modern equipment of clinics and high-class staff training, is a leader in the treatment of cancer, including astrocytoma of the brain. The appreciation of the work of Israeli specialists is not accidental, because the success of the operations is supported by modern equipment, which is regularly updated and improved, and the development of scientifically grounded effective schemes / methods for treating tumors, and the attitude to the sick, whether they are citizens of the country or visitors.

Both state and private clinics take care of their prestige, and their work is controlled by government agencies and relevant laws, which no one is in a hurry to break (a different mentality). In the hospitals and medical centers, the life and health of the patient comes to the fore, and both the medical staff and special international organizations take care of it. Patient support and patient support services help you get settled in a foreign country, quickly and efficiently complete the necessary research, and offer opportunities to reduce the cost of the services offered if financial difficulties arise.

The patient always has a choice. At the same time, the lower price of services does not mean their poor quality. In Israel, not only private, but also public clinics can boast fame throughout the world. Moreover, this fame is deserved by many successful operations and many lives saved.

Considering the best clinics in Israel for the treatment of astrocytomas, it is worth noting the following government institutions:

• Hadassah University Hospital in Jerusalem. The clinic has a department for the treatment of cancer of the central nervous system. In the neurosurgical department, patients are provided with a full range of diagnostic services: examination by a neurologist, radiography, CT or MRI, electroencephalography, ultrasound (prescribed for children), PET-CT, angiography, spinal puncture, biopsy along with histological examination.

Astrocytomas of various degrees of malignancy are performed by world-famous neurosurgeons who specialize in treating cancer patients. Tactics and treatment regimens are selected individually, which does not prevent physicians from adhering to evidence-based treatment protocols. The clinic has a neuro-oncological rehabilitation department.

• Medical Center them. Suraski (Ichilov) in Tel Aviv. One of the largest public institutions in the country that are ready to accept foreign patients. At the same time, the indicators of the effectiveness of cancer treatment are simply amazing: 90% of the effectiveness of cancer treatment in combination with 98% of successful operations on the brain. Ichilov Hospital is included in the TOP 10 most popular clinics. It offers a comprehensive examination and management of several specialists at once, quick preparation of a treatment plan and calculation of its cost. All the doctors working in the hospital have high qualifications, have been trained in well-known clinics in the USA and Canada, have a large stock of up-to-date knowledge and sufficient practical experience in treating cancer patients. Operations are carried out under the control of neuronavigation systems, which minimizes possible complications.
• Medical Center them. Yitzhak Rabin. Multidisciplinary medical institution equipped with the largest oncological center "Davidov" in accordance with the latest technologies. The fifth part of cancer patients in Israel is being treated in this very center, which is famous for the high accuracy of diagnosis (100%). About 34-35% of diagnoses made by hospitals in other countries are disputed here. People who considered themselves incurably sick, get a second chance here and the most valuable thing is hope.

In the treatment of cancer patients apply the latest developments, targeted and immunotherapy, robotics. During treatment, patients live in hotel-type wards.

• State Medical Center "Rambam". A modern well-equipped center, specialists of the highest category, extensive experience in treating patients with brain tumors, good attitude and care for patients regardless of their country of residence - this is an opportunity to get quality treatment in a short time. It is possible to contact the hospital without intermediaries and after 5 days have already flown for treatment. There is a possibility of participation in experimental methods for patients with a poor prognosis of treatment with traditional methods.
• Sheba Medical Center. Well-known state university hospital, which for many years cooperates with the American Cancer Center. M.D. Anderson. In addition to good equipment, high accuracy of diagnostics and successful operations to remove brain astrocytomas, the clinic's special feature is the special care program for patients, which includes constant psychological support.

As for private clinics, where you can undergo qualified and safe treatment of brain astrocytomas, you should pay attention to such a multi-purpose Assuta clinic in Tel Aviv, which is built on the basis of the institute. Is it worth mentioning that this is one of the most famous and popular clinics, the cost of which is comparable to those in public hospitals and is controlled by the state. Accurate diagnosis, modern methods of treatment of brain cancer, a high percentage of recovery at stage 1 cancer (90%), the highest level of laboratory equipment, diagnostic rooms, operating rooms, comfortable conditions for patients, professionalism of all doctors and nurses involved in the treatment of the patient.

A feature of almost all private and public hospitals in Israel is the professionalism of physicians and prudent, caring attitude towards patients. Today there are no special problems in terms of communication and registration for treatment in Israel (with the exception of financial ones, because foreign patients are being treated there for a fee). With regard to payment of treatment, it is mainly carried out on the fact, and in addition there is the possibility of installment.

High competition, state control and sufficient funding are forcing Israel’s clinics, as they say, to keep the brand. We have no such competition, as there is no opportunity to carry out accurate diagnosis and quality treatment. We have good doctors who are powerless in the face of the disease, not because of a lack of knowledge and experience, but because of the lack of necessary equipment. Patients would like to believe their domestic specialists, but they cannot, because their lives are at stake.

Today, the treatment of brain tumors in Israel is the best way to take care of yourself or your relatives, whether it is a question of brain cancer, or there is a need to operate on other vital organs.