Stereotactic radiotherapy. Stereotactic radiotherapy. Combination of repeated stereotaxic irradiation in hypofractionation mode for relapses of head and neck cancer with systemic treatment

Stereotactic radiotherapy of oncological diseases is one of the effective methods of oncological diseases treatment organized by our center. Stereotactic radiosurgery (SRS) takes place (despite the name) without a surgical scalpel, this radiation therapy technology does not "cut out" the tumor, but damages the DNA of the metastasis. Cancer cells lose their ability to reproduce, and benign formations are significantly reduced in 18-24 months, and malignant ones are much faster, quite often within 60 days.

Stereotactic radiotherapy is used to treat the following cancers:

• pancreatic, liver and kidney cancer;
• tumors of the brain and spinal column;
• prostate and lung cancer.

SRS provides extreme accuracy of exposure to the affected organ, without the danger of damage to neighboring tissues and organs. The accuracy of radiation delivery is based on the following components of stereotaxis technology:

localization using three-dimensional visualization allows you to set the exact coordinates of the tumor (target, target) in the body;

equipment for fixing the patient in a fixed position during the procedure;
sources of gamma or x-ray radiation allowing to focus the rays directly on the pathology;

visual control of radiation delivery to the affected organ before the procedure, correction of the direction of the rays during the procedure.

Stereotactic radiotherapy as an alternative to invasive surgery

Invasive surgery involves the penetration of pathology through healthy organs and tissues, that is, intervention through the skin, mucous membranes and other external barriers of the body, damaging them accordingly. For tumors and various vascular anomalies located near vital organs or pathologies deep in the brain, intervention is undesirable.

Stereotaxis treats pathologies with minimal impact on neighboring tissues, it is mainly used in the treatment of neoplasms of the brain and spine, but it is also used in the treatment of arteriovenous diseases. Radiation exposure to arteriovenous malformations (AVMs) leads to their thickening and disappearance within a few years.

The absence of damage makes it possible to use the stereotaxic technique not only in neurosurgery, but also in studies of the functioning of the deep structures of the brain.

The stereotactic technique (from the Greek: "stereos" - space, "taxis" - location) provides the possibility of low-traumatic access to all parts of the brain, and is a complex technology for the treatment of oncological diseases based on radiotherapy, mathematical modeling, and the latest achievements of neurosurgery.

Today, about half of cancer patients are treated with radiation therapy. This treatment, which was developed at the turn of the 20th century, uses the power of radiation to kill cancer cells while trying to avoid harming nearby healthy tissue.

Radiation therapy for cancer in Israel has come a long way since its inception. Recent advances have allowed physicians to develop a safer and faster method called hypofractionated radiotherapy, which is helping physicians cut radiation courses by nearly half, significantly reducing the total amount of radiotherapy a patient needs. Having fewer sessions of radiation therapy can improve patients' quality of life - fewer treatments can mean fewer unpleasant side effects such as skin irritation, loss of appetite, nausea and fatigue that are often associated with cancer treatments. It also means fewer trips to the cancer center.

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In some cases, a higher dose given in fewer sessions may be a more effective cancer treatment.

While conventional radiation therapy delivers a small amount of radiation to a patient for nine weeks, hypofractionated radiation therapy delivers large doses or fractions of radiation, often in about five weeks, and sometimes in as little as a few days. Stereotactic radiotherapy (SBRT), a precise, high-dose form of hypofractionated radiotherapy, allows doctors to treat cancer in as little as one to five treatments.

In part, rapid radiation treatments are effective because advanced technology helps physicists calculate the correct dose of radiation and precisely position the patient to receive it so that the radiation beams are targeted only at tumors. The goal is to leave as many healthy surrounding cells as possible untouched by radiation.

The ability to maintain a patient's quality of life is improving with every advance in radiation technology.

Advances include high-tech computing software, technology that helps protect nearby body parts from radiation, and 4-D scans for treatment planning. This ability is better than it was five years ago and a big leap beyond what was available 10 years ago.

However, rapid radiotherapy is not an option for all patients or even all cancers. Radiation oncologists prescribe hypofractionation for patients undergoing prostate, gastrointestinal, lung, and breast cancer treatments.

Treatment of prostate cancer in Israel

Treatment Time: The standard treatment for prostate cancer in Israel is a course of 44 treatments over a period of nine weeks. With hypofractionated radiation therapy, patients are prescribed five treatments over two weeks.

New Advances: Radiation therapy is a common treatment for prostate cancer. However, radiation can damage the rectum, which is close to the prostate gland. Protecting the rectum is important; if it is damaged, the person may experience incontinence.

New technologies have "opened the door" for the safe and rapid treatment of prostate cancer. One of them, SpaceOAR, is essentially a gel spacer that helps keep the rectum away from the prostate during radiation therapy. This creates another layer of security by placing fluid between the prostate and rectum, effectively protecting the rectum from very high doses of radiation.

Israeli doctors also use advanced technology to track the natural movement of the prostate during radiation therapy. This is a 4-D tracking system that uses micro-sized transponders that are implanted into the prostate by a urologist during a quick outpatient procedure. If the prostate moves during treatment, the transponders "sound the alarm" which alerts the radiation oncology team. Treatment is automatically stopped until the technicians make the necessary adjustments to protect the areas around the prostate, especially the rectum and bladder.

The combination of advanced SpaceOAR technology and RF tracking allows for highly secure SBRT of the prostate.

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Who is it for: rapid radiotherapy (hypofractionated radiotherapy) is suitable for most patients undergoing prostate cancer treatment in Israel. Exceptions are men with severe urinary symptoms (faster treatment has slightly higher short-term urinary side effects, such as inflammation and bladder obstruction). Also, this method is not used for men who need androgen deprivation therapy (hormone therapy that suppresses testosterone) or who need radiation to regional lymph nodes.

Treatment of gastrointestinal cancer in Israel

Treatment Time: Gastrointestinal cancer occurs in the esophagus, stomach, biliary system, pancreas, small intestine, colon, rectum, and anus. When undergoing gastric cancer treatment in Israel or intestinal cancer treatment in Israel with standard radiotherapy, patients receive treatment five days a week for about six weeks. However, SBRT reduces the number of treatments to five, a high dose. This faster approach to gastrointestinal cancer treatment in Israel also eliminates the need for concurrent chemotherapy.

New Advances: Use of 4D Knife Computed Tomography for Treatment Planning - Essentially a video showing tumor movement as the patient breathes, these 4D planning CT scans allow the radiation field to be focused on the exact area occupied by tumors during the respiratory cycle. Technologies are also being used to limit the movement of the tumor from breathing and to track the movement of tumors during treatment.

Who is it for: For patients who are not receiving chemotherapy, SBRT is an option for treating gastrointestinal cancer in Israel in cases where there is no pancreatic cancer or it can be partially removed during surgery, or for patients who cannot have surgery for other medical reasons. . It is also an option for patients with recurrent swelling in the same area after surgery. SBRT is also used in patients with primary liver tumors (such as hepatocellular carcinoma and cholangiocarcinomas) and in patients with a limited number of liver metastases.

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Treatment of lung cancer in Israel

Treatment time: Early stage lung cancer treatment in Israel with standard radiotherapy is about seven weeks of exposure. This time can be reduced to three to five treatments over two weeks, and patients with advanced cancer who do not metastasize can be treated in about four weeks.

New advances: The use of high-precision imaging technology allows more precise targeting of radiation to tumors, allowing higher doses of radiation to be delivered in a shorter number of courses.

Who it's for: Patients with cancer limited to the thoracic region who are not going to take chemotherapy may be candidates for hypofractionated radiotherapy.

Breast Cancer Treatment

Treatment Time: For early stage breast cancer treatment in Israel, the standard consists of either a mastectomy or breast conservation (also known as breast conserving surgery or lumpectomy) followed by five to seven weeks of breast radiation. Hypofractionated radiotherapy is now recommended for some patients. The side effects of the shorter course treatment are also equivalent if not better than the standard treatment.

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The course of treatment for hypofractionated radiation therapy for breast cancer is to deliver a slightly larger daily dose of radiation five days a week, with about 15 fractions for four weeks instead of 33 fractions for seven weeks. “Ultimately, the total dose received with hypofractionated therapy is equivalent and produces similar results and side effects.

New Advances: A technology called Deep Inspiration Breath-Hold (DIBH) makes chest radiotherapy safer for patients with left-sided breast cancer by reducing the effect of radiation on the heart. When radiation is aimed at the entire chest or chest wall, the radiation beam destroys all tissue it comes into contact with. In left-sided breast cancer patients, parts of the heart and lungs located under the chest are sometimes exposed to the radiation beam. With the DIBH technique, radiation is delivered only when the patient takes a deep breath and in a precise position that expands the chest and safely moves the heart out of the radiation beam.

Who it's for: Hypofractionated breast irradiation is the recommended treatment for a select group of patients with early breast cancer.

With hypofractionated radiotherapy, cancer treatment is becoming faster and easier for patients with prostate, gastrointestinal, lung, and breast cancer. And clinical trials are currently underway to determine whether faster treatment times will effectively treat other types of cancer.

Stereotactic radiotherapy or stereotaxic radiosurgery allows, avoiding exposure to healthy brain tissue, to deliver targeted radiation directly to small tumors. The destruction of the tumor occurs as accurately as when working with a surgical scalpel.

Advantages of stereotactic radiotherapy:

• The technique allows targeted, high-dose radiation to be delivered to gliomas less than 3 cm (or 1.25 inches) in diameter without damaging surrounding tissues.
• Stereotactic radiosurgery allows you to reach small tumors located deep in the brain tissue, which were previously considered inoperable.
• In some cases, stereotactic radiosurgery is the only treatment required.
• Stereotactic radiation can be repeated, unlike traditional radiation therapy. Therefore, stereotactic radiosurgery is used for tumor recurrence, when the patient has already undergone standard radiotherapy.
• The combined use of stereotaxic radiosurgery and techniques that control speech and other mental functions in patients who remain conscious during the procedure ensures the safe removal of tissue with minimal risk of impairment of these functions.

Typically, radiosurgery begins with a series of steps to determine the purpose of the radiation:

• First, local anesthesia is administered. During a standard operation, the patient's head is carefully fixed in a stationary state with the help of a stereotaxic frame, which is screwed to the skull. (The use of the frame is effective only for brain tumors with the correct contours). The frame is removed immediately after the procedure is completed (after 3-4 hours).
• Magnetic resonance imaging creates a three-dimensional map of the patient's brain.
• The computer program calculates the level of exposure and areas for targeting exposure.

Improving imaging techniques allow the use of frameless stereotaxic operations, which are effective in a greater number of tumors.

Treatment begins after the completion of the preliminary planning stage. Various sophisticated devices such as the Gamma Knife and the Adapted Medical Linear Accelerator (LINAC) are used to deliver a narrowly focused beam of beams in stereotactic radiosurgery. In fact, the treatment time takes from 10 minutes to 1 hour.

• Gamma Knife technology uses gamma rays that radiate from multiple directions and converge at a single point on the tumor. Each individual gamma ray has a low dose of radiation, but when the rays converge, the intensity and destructive power of the beam increases significantly. The Gamma Knife is only used on very small tumors and is therefore usually used as an adjunct procedure after standard radiotherapy, surgery, chemotherapy, or a combination of the two.
• The linear accelerator (LINAC) generates protons (positively charged particles) whose beams correspond to the size of the tumor. The patient is located on a bed, the position of which can change. This procedure allows the treatment to be carried out in multiple low-dose sessions (fractionated stereotactic radiosurgery) rather than in a single session. This technique is suitable for the treatment of large tumors.

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Breast cancer treatment in Israel

Today in Israel, breast cancer is completely curable. According to the Israeli Ministry of Health, Israel currently has a 95% survival rate for this disease. This is the highest rate in the world. For comparison: according to the National Cancer Register, the incidence in Russia in 2000 compared to 1980 increased by 72%, and the survival rate is 50%.

This type of surgical treatment was developed by the American surgeon Frederick Mohs and has been successfully used in Israel for the past 20 years. The definition and criteria for Mohs surgery were developed by the American College of Mohs Surgery (ACMS) in collaboration with the American Academy of Dermatology (AAD).

SBRT is an abbreviation of English words. They mean "stereotactic corporal (referring to the torso - everything but the head) radiotherapy." Focused precisely on the tumor, a beam of super-powerful radioactive radiation makes it possible to irreversibly damage the DNA of tumor cells in one to five sessions, causing their death. At the same time, the surrounding tissues and the whole organism as a whole almost do not experience negative effects. This is due to the technological features of the method.

The need to calculate with maximum accuracy the direction and area of ​​exposure to the radiation flux, its power, to provide for tumor deviations associated with respiratory movements requires teamwork of specialists and sophisticated equipment. Each patient is treated by an oncologist-radiologist, a medical physicist, a dosimetrist, a radiologist, and a nurse.

First, a 4D CT or MRI is performed to image the tumor and pinpoint its location during the respiratory cycle, which is especially important in the treatment of lung and abdominal tumors. Then, under the control of imaging techniques, radiopaque markers are injected into the tumor. This is done in a minimally invasive endoscopic or laparoscopic way.

The next stage is the modeling of radiotherapy. Individual fixing devices are prepared for each patient, so that during the session the only possible movements are only respiratory ones. The tumor is re-analyzed in a four-dimensional image already during the patient's stay in the fixing device.

At the third stage, during treatment planning, using computer programs, hundreds of thousands of variants of the radiation beam course are evaluated, achieving the maximum correspondence of the shape of their focus to the shape of the tumor and synchronizing them with its movement during breathing. Continuous irradiation or pulsed irradiation can be provided - only during inhalation or exhalation.

The final stage is the actual radiotherapy session. It is carried out using a linear accelerator. The patient is on an associated manipulation table. Numerous outgoing radioactive rays at different angles are individually low power and do little or no harm on their way to the tumor. But in it they are focused and have a powerful effect, destroying the DNA of tumor cells, the endothelium of the blood vessels that feed it, and mutated stem cells. In the tissues adjacent to the tumor, the beam power drops sharply. It is precisely for the full coverage of the entire tumor mass and the prevention of damage to healthy tissues adjacent to it that such careful planning of the procedure, down to fractions of a millimeter, is necessary.

Stereotactic SBRT radiation therapy is often effective in tumor recurrence, while classical radiotherapy methods in such cases are most often ineffective. In addition, it is shown if:

• the tumor is located in an area that is difficult to access for surgical treatment
• the operation is not possible due to comorbidities or patient refusal
• the tumor is adjacent to vital anatomical structures
• when exposed to the tumor, movements cannot be excluded, for example, respiratory

The best effect of SBRT stereotactic radiation therapy is obtained in patients with primary and metastatic tumors that are not too numerous (no more than 3-5 foci) up to 5-6 cm in size. Most often these are tumors:

• lungs
• lymph nodes
• liver
• kidney
• prostate
• vertebrae and perivertebral tissues
• pancreas

Stereotactic SBRT is contraindicated if:

• there are general contraindications to radiotherapy - cancer cachexia, severe anemia, inhibition of leukocyte production, autoimmune disease, decompensation of severe diseases of internal organs - heart, lungs, liver, kidneys, serious complications of the tumor process (for example, bleeding)
• the tumor is radioresistant, that is, insensitive to x-rays
• the tumor has no clear boundaries and infiltrates (penetrates) the surrounding tissues. Due to the critical drop in the power of the radioactive beam at the border of the irradiated zone, in such cases it is impossible to provide a full impact on tumor cells and save healthy structures in the border area

Usually spend from one to five sessions lasting 30-60 minutes. The high power of the radioactive flow makes it possible to suppress the tumor focus in a short time, while traditional radiotherapy lasts several weeks and even months. The classical technique does not allow simultaneous exposure to high doses due to the pronounced general negative effect of radiation on the body.

Benefits of SBRT stereotactic radiotherapy:

• Highly effective radiotherapy technique, often as good as surgical methods
• short course of treatment
• Minimal involvement of healthy tissues and minor side effects
• Can be used after an ineffective course of classical external irradiation
• Allows you to return to a normal lifestyle almost immediately, does not require long-term rehabilitation

S. I. Tkachev, S. V. Medvedev, D. S. Romanov, P. V. Bulychkin, T. V. Yuryeva, R. A. Gutnik, I. P. Yazhgunovich, A. V. Berdnik, and Yu. B.

The emergence of innovative technical developments: three-dimensional planning, the use of a multi-leaf collimator, modeled by the intensity of radiation therapy, more advanced methods of fixation, have significantly increased the possibility of accurately summing up and escalating the dose of ionizing radiation to a selected volume. This has changed the understanding of the role of radiation therapy in the treatment of liver metastases. The data of foreign authors indicate the possibility of achieving 95% local control one year after stereotaxic radiotherapy, 92% - two years later (and 100% for tumors smaller than 3 cm) with the development of radiation damage of the third and higher degree in only 2% of cases. In 2011, after the technical re-equipment of the Federal State Budgetary Institution of Russian Cancer Research Center named after N.I. N. N. Blokhin of the Russian Academy of Medical Sciences, in clinical practice for the treatment of patients with liver metastases, the technique of local stereotactic radiosurgery (SBRS) began to be introduced. The technique allows you to create a high dose of ionizing radiation locally in a metastatic tumor node and cause destruction of the tumor. This promising direction in the treatment of metastatic liver cancer has significantly expanded the possibilities of combined treatment. The article provides a review of the literature on the treatment of liver metastases, we also publish the results of the use of stereotactic radiosurgery in thirty-five patients with liver metastases and a clinical case of the successful use of this technique in a somatically aggravated patient.

Key words: liver metastasis, stereotactic radiosurgery, local control.

Contact Information:

S. I. Tkachev, S. V. Medvedev, D. S. Romanov, P. V. Bulychkin, T. V. Yurieva, R. A. Gutnik, I. P. Yazhgunovich, A. V. Berdnik, Yu. B. Bykova - Department of Radiology, Department of Radiation Oncology (Head - Prof. S. I. Tkachev) N. N. Blokhin, RAMS, Moscow. For correspondence: Romanov Denis Sergeevich, [email protected]

Introduction

During autopsy, metastatic foci in the liver are found in 30% of patients with oncological diseases. For the treatment of patients with multiple liver metastases (more than three foci), systemic and / or regional drug therapy is preferable. In patients with limited liver damage, it is possible to use local methods of treatment, such as: surgical resection, radiofrequency thermal ablation, chemoembolization, radioembolization, cryodestruction, ethanol administration,

microwave coagulation, laser thermal destruction, electrolysis of metastases. Each of these approaches has its advantages and disadvantages, but only stereotactic radiotherapy can be used if there are contraindications for the use of the above methods.

For a long time, radiation therapy was considered an unpromising technique for the treatment of liver metastases. The use of such a technique as total irradiation of the liver has not proven to be effective and safe, as, for example, irradiation of the entire brain in the case of metastatic

OF MALIGNANT TUMOURS

damage to this organ. With the improvement of the scientific and technological base of radiation therapy: the advent of new technologies for delivering a dose of ionizing radiation, planning systems, verification of plans for remote radiation therapy, visualization, fixation of patients, the development of radiobiology - radiation oncologists received a formidable weapon in the fight against metastatic liver disease - stereotactic radiosurgery of neoplasms of the indicated organ.

Stereotactic radiosurgery

In the 90s of the last century, the first works appeared in foreign literature on the advisability of performing local stereotactic radiosurgery (stereotactic body radiation surgery - SBRS) for single (up to 3 foci) liver metastases.

In connection with the biological characteristics of metastatic liver damage in colon cancer, patients in this group are separated into a separate subgroup. Liver resection is the gold standard for local treatment of liver metastases, in particular colorectal cancer metastases. Several large studies show a 50% overall survival rate five years after surgery. Historically, it was considered possible to perform liver resection in those situations where it is possible to completely remove a limited number of metastases with a negative resection margin of more than one centimeter and the volume of the liver remaining after the operation, sufficient for adequate functioning of the organ (at least 30% of the total functional volume of the liver). If these criteria are followed, resection is possible in 30-40% of patients who need it. At the moment, it is possible to simultaneously remove more than seven metastases from the liver, it has been established that the width of the negative resection margin does not affect the local control and patient survival. In large centers dealing with this problem, the risk of postoperative complications and mortality is reduced to minimal values. Moreover, repeated resections for recurrent liver cancer are quite safe.

and offer the same survival benefits as first-time resection. Unfortunately, patients with synchronous bilobar, large, localized in inconvenient for surgical intervention metastases and extrahepatic manifestations of the disease, those whose resection does not leave the necessary 30% of the liver, patients over seventy years of age and burdened somatically, are often recognized as unresectable, and following this logic, uncurable. In addition, there are no randomized trials comparing the effect of resection versus conservative non-surgical local therapy in resectable patients.

The emergence of innovative technical developments (three-dimensional planning, multileaf collimator, radiation therapy with intensity modulated radiation therapy (IMRT), more advanced methods of fixation), which significantly increased the possibility of accurately supplying ionizing radiation to a selected volume, and consequently, supplying a higher dose to the volume of the tumor, changed the idea of ​​the role of radiation therapy in the treatment of liver metastases. A variant of high-precision radiotherapy in which an ablative dose is delivered in 1-5 fractions is called stereotactic radiotherapy. When used extracranially, this type of radiation therapy is called stereotactic body radiation surgery (SBRS). As defined by ASTRO, SBRS involves the delivery of high doses of ionizing radiation with high conformity and a sharp dose gradient in surrounding normal tissues in a small number of fractions (two to six) to tumors located outside the brain.

There are many publications regarding the use of SBRS for the treatment of malignant liver lesions, which show encouraging results. The earliest of them date back to 1994-1995. In this paper, investigators report the first results of SBRT on 42 extracranial tumors.

in 31 patients. 23 patients underwent radiotherapy for liver metastases (14 patients) or hepatocellular carcinoma (9 patients). Most of the patients had solitary tumors in the liver, lungs and retroperitoneal space. Their volumes of subclinical tumor spread (CTV - clinical target volume,) ranged from 2 to 622 cm in 14.2 Gy), were brought for 1-4 fractions. Researchers noted local control in 80% of cases during the subsequent life of patients, which lasted from 1.5 to 38 months. In addition, the disappearance or reduction of tumors in size was noted in fifty percent of cases. The median follow-up period was 10 months for patients with hepatocellular carcinoma (range 1 to 38 months) and 9 months for patients with liver metastases (range 1.5 to 23 months).

In 1998, the same research group reported on the experience of using stereotaxic radiosurgery for the treatment of primary malignant and metastatic liver tumors, SOD was from 15 to 45 Gy summed up in 1-5 fractions. Fifty patients with 75 tumors were treated. Treated volumes ranged from 2 to 732 cm3 (with an average of 73 cm3). During follow-up, with a median of 12 months (values ​​ranged from 1.5 to 38 months), about 30% of the tumors stabilized, about 40% of the tumors shrank, and 32% completely regressed. Four (5.3%) tumors were interpreted as local failures. Unfortunately, the average life expectancy was only 13.4 months (with values ​​ranging from 1.5 to 39 months), with the predominant causes of death from progressive liver cirrhosis or extrahepatic progression of the underlying disease.

doses of 20 Gy (two fractions) or 15 Gy (three fractions). Within the follow-up period from 13 to 101 months, local control over all recurrent tumors was achieved with complete regression of metastases in two cases. Only one patient had local progression of the disease in the form of damage to two lobes of the organ, which was preceded by extrahepatic spread of the disease. One patient subsequently died of non-oncological causes in the absence of signs of the underlying disease, two died from generalization of the malignant process, and one patient at the end of the study had been in remission for 101 months after stereotaxic radiosurgery.

Dawson et al. performed SBRT on 16 patients with liver metastases and 27 patients with primary hepatocellular carcinoma using 3D conformal radiation therapy at a mean dose of 58.5 Gy (28.5 to 90 Gy) at 1.5 Gy per fraction twice daily. There was one case of grade III RILD and no treatment-related deaths. In a more recent study by Dawson et al. modeled the possibility of developing complications from normal tissues for the development of RILD within 4 months after conformal radiation therapy for liver metastases or intrahepatic hepatobiliary tumors. The study demonstrated a significant effect of volume and mean single focal dose on predicting the development of RILD in multivariate analyses. Other significant predisposing factors for the development of RILD were primary liver disease (cholangiocarcinoma and hepatocellular carcinoma versus metastatic disease) and male gender. It was noted that these patients were also receiving concurrent topical chemotherapy and the use of bromodeoxyuridine (versus fluorodeoxyuridine) was also associated with an increased risk of developing RILD. There were no cases of RILD development when the average total focal dose of less than 31 Gy was administered to the liver.

In 2001 Herfarth et al. conducted a study that examined the effect of

Possibilities of stereotactic radiosurgery in the treatment of patients with liver metastases

efficacy of SBRS in 37 patients with 60 liver lesions. The absorbed dose was 26 Gy and the size of the tumors ranged from 1 to 132 cm3 with an average of 10 cm3. All patients tolerated the treatment well, SBRS did not lead to any case of significant side effects. Eleven patients reported intermittent loss of appetite or mild nausea within one to three weeks after the end of treatment. None of the treated patients developed clinically detectable radioinduced liver disease. As a result of SBRS for 5.7 months (ranged from 1 to 26.1 months), fifty-four of fifty-five (98%) tumors showed a positive effect, according to computed tomography performed after 6 weeks (22 cases of disease stabilization, 28 cases of partial response and 4 cases of complete response). The local positive effect was 81% within 18 months after the end of treatment.

Wulf et al. reported the results of SBRS in five patients with primary liver cancer and 39 patients with 51 liver metastases performed at the University of Wurzburg. Twenty-eight tumors were assigned to the so-called "low dose" group in three fractions of 10 Gy (27 patients) or four sessions of 7 Gy (1 patient). In addition, there was the so-called "high dose" group, in which patients were subjected to SBRS with single doses of 12-12.5 Gy in three fractions (19 patients) or 26 Gy per fraction (9 patients). Median follow-up was 15 months (range 2 to 48 months) for primary liver cancer and 15 months (range 2 to 85 months) in patients with liver metastases. In all cases of primary malignant liver disease, a positive effect was achieved, including true stabilization. Among fifty-one metastases, 9 cases of local recurrence were noted within a period of three to 19 months. There was a delimiting significant correlation between total radiation dose and local control scores (p=0.077) with local control scores of 86% and 58% at 12 and 24 months.

in the "low dose" group versus 100% and 82% in the "high dose" group, respectively. There were no cases of radiation damage of III or higher degrees of RTOG-EORTC. In multivariate analysis, high dose versus low dose was the only significant predictor of local control scores (p = 0.0089). Overall survival at one and two years among all patients was 72% and 32%, respectively. The authors conclude that SBRS for primary malignant diseases and metastatic liver tumors is an effective local treatment without significant complications for patients who were denied surgery.

In a study by Hoyer et al. , the results of the use of SBRS in the treatment of colorectal cancer metastases are presented. Sixty-four patients with a total of 141 colorectal cancer metastases in the liver (44 patients) or lungs (20 patients) were subjected to SBRS in three fractions of 15 Gy for five to eight days. The median follow-up was 4.3 years, and after two years, local control rates were 86%. Radiation toxicity in most cases was moderate, however, three cases of serious adverse events and one death were recorded. The researchers concluded that SBRS for inoperable colorectal cancer metastases is not inferior to other methods of local ablation of metastases.

Somewhat later, Schefter et al. reported preliminary results from a multicenter phase I study of SBRS in patients with liver metastases. Patients had one to three liver metastases, with a maximum tumor diameter of less than six centimeters, and adequate liver function. Some patients were subjected to SBRS at a total dose of 36 Gy in three fractions. Another part of the patients received higher doses of radiation up to 60 Gy in three fractions. At least 700 milliliters of healthy liver tissue should have received a total dose of less than 15 Gy. Dose-limiting toxicity was chosen as manifestations of acute radiation damage to the liver or intestines of the III degree or any manifestations of acute radiation damage.

denia IV degree. None of the patients had dose-limiting radiation injury, so the radiation dose was raised to 60 Gy in three fractions. Twelve of 18 patients were alive at the time of the investigators' analysis, with a median of 7.1 months after entry into the protocol.

The study was continued in 2006 by Kavanagh et al. reported the results of a phase I/II analysis of a prospective study of the use of SBRS for the treatment of liver metastases. In this case, the study included patients with no more than three tumors with a maximum diameter of less than six centimeters. The total focal dose was 60 Gy in three fractions for three to fourteen days. In 2006, interim results of 36 patients with SBRS were published: 18 from the first phase and 18 from the second phase. Among 21 patients with a follow-up period ranging from six to 29 months, there was only one case of third-degree radiation injury RTOG associated with the performed SBRS, which occurred in the subcutaneous tissues. No cases of radiation toxicity of the fourth degree were recorded. The researchers noted that for 28 lesions over eighteen months, the positive effect, including true stabilization, was 93%.

In 2009, Rusthoven et al. published the results of a multicentre (conducted between August 2003 and October 2007 in 7 hospitals) phase I/II study of the use of SBRS in patients with liver metastases. The study included patients with 1-3 liver metastases and the maximum size of individual nodes less than 6 cm. The initial level of bilirubin, albumin, prothrombin and APTT, and liver enzymes were taken into account. 14 days of chemotherapy before and after SBRS were not allowed. For 49 metastatic lesions, local control rates were 95% (one year after SBRS) and 92% (two years after SBRS). In 2% of patients, radiation injuries of the third and higher degrees were detected with a median of 7.5 months after stereotactic radiosurgery. The two-year rate of positive local effect for metastases up to 3.0 cm in diameter was equal to

100%. This is the highest reported benefit rate despite a 2-year survival rate of 30%. The authors conclude that stereotaxic radiosurgery with a total dose of 60 Gy per three fractions is both safe and effective for the treatment of patients with one to three liver metastases.

Van der Pool et al. presented a study in 2010 in which 20 patients with liver metastases received SBRS at doses ranging from 30 to 37.5 Gy in three fractions. One hundred percent indicators of a positive local effect were obtained one year after the treatment. After two years, this rate dropped to 74%, with a median survival of 34 months. Among the radiation injuries, one case of a rib fracture and 2 cases of an increase in liver enzymes of the III degree are noted as long-term consequences of radiation therapy.

Also in 2010, the results of a prospective study by Goodman et al. , in which 26 patients with malignant liver tumors (19 of them with metastatic lesions) underwent SBRS with one fraction in the amount of 18-30 Gy. Local effect rates after 12 months were 77%. The two-year survival rate for patients with liver metastases was 49%.

In 2011, after technical re-equipment, in the Federal State Budgetary Institution of Russian Cancer Research Center named after. NN Blokhin RAMS in clinical practice for the treatment of patients with liver metastases introduced the technique of local stereotactic radiosurgery (SBRS). The technique allows you to create a high dose of ionizing radiation locally in a metastatic tumor node and cause destruction of the tumor. This promising direction in the treatment of metastatic liver cancer has significantly expanded the possibilities of combined treatment.

From August 2010 to July 2013 in the radiology department of the Federal State Budgetary Institution of Russian Cancer Research Center. N. N. Blokhin RAMS SBRS conducted thirty-five patients with liver metastases of tumors of various histological structures. A single focal dose varied from ten to twenty grays, radiosurgery was performed

Possibilities of stereotactic radiosurgery in the treatment of patients with liver metastases

for three sessions within 5-7 days. Two patients did not provide follow-up examination data, and in two more cases, local progression was recorded. Seven patients had complete tumor regression, thirteen had partial tumor regression, and eleven had stabilization of the treated lesions. Five patients subsequently developed new metastatic lesions in untreated areas of the liver. The median follow-up was 17 months. In none of the cases, early and late radiation injuries of III-IV degrees were recorded, the frequency of development of radiation injuries of II degree was 9%.

Conclusion

Only with the availability of modern equipment and technologies, there are prospects for the use of stereotactic radiosurgery in the treatment of patients with liver metastases. This technology is a real alternative to other methods of local impact on metastatic formations. The given data of foreign authors, as well as the experience of the radiological department of the Federal State Budgetary Institution of Russian Cancer Research Center named after N.N. N. N. Blokhin of the Russian Academy of Medical Sciences testify to the high efficiency and safety of this technology, even in those patients who are denied other methods of treatment.

Clinical case

Patient A. 65 years old. Sigmoid colon cancer, liver metastasis, T4N1M1, stage IV.

On June 7, 2010, the patient underwent palliative resection of the sigmoid colon. 07/29/10 - left hemihepatectomy, resection of the right lobe of the liver.

Histological examination revealed adenocarcinoma.

After the operation, 8 courses of chemotherapy were carried out.

In August 2011, according to ultrasound data from 08/15/11, the progression of the disease in the form of a solitary metastasis in the remaining part of the liver was revealed.

By November 17, 2011, 7 courses of chemotherapy were performed.

According to the CT data of October 26, 2011, a mass up to 2.7x2.5 cm was detected between the portal and right hepatic veins, in the VII segment the focus was up to 0.9 cm (Fig. 1).

According to MRI data from 12/14/11 in the resection area in the S5-S8 segments, the node is up to 1.8 cm, closely adjacent to the portal vein. In segments S6-7, a node up to 0.5 cm is determined.

From December 21, 2011 to December 27, 2011, a course of stereotactic radiosurgery was performed on both lesions in the liver using the IMRT technique, ROD 15 Gy, 3 times a week, SOD 45 Gy.

The patient was fixed using an individual vacuum mattress,

The verification of the irradiation program was carried out using the technology of computed tomography in a conical beam on the table of a linear accelerator in the treatment position.

According to the CT data of May 15, 2012, a new lesion appeared in S6 of the liver, up to 1.7 cm in size. Two foci subjected to stereotactic radiotherapy are not visualized (Fig. 2).

Subsequently, the patient received treatment in South Korea. In July 2012 and February 2013, radio frequency

ablation of the focus in S6 of the liver. The patient noted an increase in body temperature for a long time, an abscess was detected at the site of metastasis in S6 of the liver. On August 21, 2013, a surgical intervention was performed: in the visualized areas of the liver without signs of a malignant process, in the area of ​​the resected focus in the S6 segment - tumor cells along the resection edge.

The patient is currently alive. According to the examination of August 2013, no signs of the disease were found.

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