Radiation therapy for cancer

Radiation therapy for cancer is a method of treatment using ionizing radiation. Currently, about 2/3 of cancer patients need this kind of treatment.

Radiation therapy with cancer is prescribed only with morphological verification of the diagnosis, it can be used as an independent or combined method, as well as in combination with chemotherapeutic drugs. Depending on the stage of the tumor process, the radiosensitivity of the neoplasm, the general condition of the patient, treatment can be radical or palliative.

[1], [2], [3], [4], [5], [6], [7], [8]

What is radiation therapy for cancer?

At the heart of the use of ionizing radiation for the treatment of malignant neoplasms is a damaging effect on cells and tissues, leading to their death in the production of appropriate doses.

Radiation death of cells is primarily associated with the damage of DNA-nucleus, deoxynucleoproteins and DNA-membrane complex, gross violations in the properties of proteins, cytoplasm, enzymes. Thus, in irradiated cancer cells, disturbances occur in all parts of the metabolic processes. Morphologically, changes in malignant neoplasms can be represented in three consecutive stages:

1. damage to the neoplasm;
2. its destruction (necrosis);
3. replacement of dead tissue.

The death of tumor cells and their resorption do not occur immediately. Therefore, the effectiveness of treatment is more accurately assessed only after a certain period of time after its completion.

Radiosensitivity is an intrinsic property of malignant cells. All organs and tissues of a person are sensitive to ionizing radiation, but their sensitivity is not the same, it varies depending on the state of the organism and the effect of external factors. The most sensitive to radiation is hematopoietic tissue, glandular apparatus of the intestine, epithelium of the gonads, skin and lens eye bags. Further on the degree of radiosensitivity are endothelium, fibrous tissue, parenchyma of internal organs, cartilaginous tissue, muscles, nervous tissue. Some of the neoplasms are listed in order of decreasing radiosensitivity:

• seminoma;
• lymphocytic lymphoma;
• other lymphomas, leukemia, myeloma;
• some embryonic sarcomas, small cell lung cancer, choriocarcinoma;
• Ewing's sarcoma;
• squamous cell carcinoma: highly differentiated, moderate degree of differentiation;
• adenocarcinoma of the mammary gland and rectum;
• transitional cell carcinoma;
• hepatoma;
• melanoma;
• glioma, other sarcomas.

The sensitivity of any malignant neoplasm to radiation depends on the specific characteristics of its constituent cells, as well as on the radiosensitivity of the tissue from which the tumor has occurred. The histological structure is an indicative sign of the prediction of radiosensitivity. Radiosensitivity is affected by the nature of growth, the size and duration of its existence. Radiosensitivity of cells in different stages of the cell cycle is not the same. The cells with the highest sensitivity are mitosis phases. The greatest resistance is in the synthesis phase. The most radiosensitive neoplasms that originate from tissue characterized by a high rate of cell division, with a low degree of cell differentiation, are exophytally growing and well-oxygenated. More highly resistant to ionizing effects are highly differentiated, large, long-term tumors with a large number of radiation-resistant anoxic cells.

To determine the amount of energy absorbed, the concept of radiation dose is introduced. The dose is understood as the amount of energy absorbed per unit mass of the irradiated substance. Currently, according to the International System of Units (SI), the absorbed dose is measured in grams (Gy). A single dose is the amount of energy absorbed per irradiation. A tolerated (tolerable) dose level, or tolerant dose, is the dose at which the frequency of late complications does not exceed 5%. The tolerated (total) dose depends on the irradiation regime and the volume of the irradiated tissue. For connective tissue, this value is taken equal to 60 Gy with an irradiation area of 100 cm ² when irradiated daily to 2 Gy. The biological effect of radiation is determined not only by the magnitude of the total dose, but also by the time during which it is absorbed.

How is radiation therapy performed with cancer?

Radiation therapy in cancer is divided into two main groups: remote methods and contact irradiation methods.

1. Remote radiation therapy for cancer:
   • static - open fields, through the lead grate, through the lead wedge filter, through the lead shielding blocks;
   • Movable - rotary, pendulum, tangential, rotational-convergent, rotational with controlled speed.
2. Contact Radiation Therapy for Cancer:
   • intracavitary;
   • interstitial;
   • radiosurgical;
   • application;
   • close-focus X-ray therapy;
   • method of selective accumulation of isotopes in tissues.
3. Combined radiation therapy in cancer is a combination of one of the methods of remote and contact irradiation.
4. Combined methods of treatment of malignant neoplasms:
   • radiotherapy for cancer and surgical treatment;
   • radiation therapy for cancer and chemotherapy, hormone therapy.

Radiation therapy for cancer and its effectiveness can be enhanced by enhancing the radioactivity of the tumor and weakening the reactions of normal tissues. Differences in the radiosensitivity of tumors and normal tissues are called the radiotherapy interval (the higher the therapeutic interval, the higher the dose of radiation can be fed to the tumor). To increase the latter, there are several ways of selective control of tissue radiosensitivity.

• Variation of dose, rhythm and irradiation time.
• The use of radiomodifying action of oxygen - by selectively increasing the radiosensitivity of the tumor of its oxygenation and by reducing the radiosensitivity of normal tissues by the creation in them of short-term hypoxia.
• Radiosensitization of the tumor with the help of certain chemotherapeutic agents.

Many antineoplastic agents act on dividing cells that are in a certain phase of the cell cycle. Moreover, in addition to direct toxic effects on DNA, they slow down the repair process and delay the passage of a cell by a phase. In the phase of mitosis, the most sensitive to radiation, the cell is delayed by vinaalkaloids and taxanes. Hydroxyurea inhibits the cycle in the G1 phase, which is more sensitive to this type of treatment compared to the synthesis phase, 5-fluorouracil in the S phase. As a result, a greater number of cells enter the mitosis phase simultaneously, and this increases the damaging effect of radioactive radiation. Such drugs as platinum, when combined with an ionizing effect, inhibit the restoration of damage to malignant cells.

• Selective local hyperthermia of the tumor causes a violation of the processes of postradiation recovery. The combination of radioactive irradiation with hyperthermia allows to improve the results of treatment in comparison with the independent effect on the neoplasm of each of these methods. This combination is used in the treatment of patients with melanoma, colorectal cancer, breast cancer, head and neck tumors, bone and soft tissue sarcomas.
• Creation of short-term artificial hyperglycemia. Reduction of pH in tumor cells leads to an increase in their radiosensitivity due to disruption of the processes of post-radiation restoration in acid medium. Therefore, hyperglycemia causes a significant increase in the antitumor effect of ionizing radiation.

The use of non-ionizing radiation (laser radiation, ultrasound, magnetic and electric fields) plays a major role in increasing the effectiveness of such a method of treatment, as radiation therapy in cancer.

In cancer practice, radiation therapy for cancer is used not only as an independent method of radical, palliative treatment, but also much more often as a component of combined and complex treatment (various combinations with chemo-, immunotherapy, surgical and hormonal treatment).

Independently and in combination with chemotherapy, radiation therapy for cancer is most often used for cancer of the following localizations:

• Cervix;
• leather;
• larynx;
• upper parts of the esophagus;
• malignant neoplasms of the oral cavity and pharynx;
• non-Hodgkin's lymphomas and lymphogranulomatosis;
• inoperable lung cancer;
• Ewing's sarcoma and reticulosarcoma.

Depending on the sequence of application of ionizing radiation and surgical interventions, pre-, post-and intraoperative treatment methods are distinguished.

Preoperative radiotherapy for cancer

Depending on the purposes with which it is assigned, three basic forms are distinguished:

• irradiation of operable forms of malignant neoplasms;
• irradiation of inoperable or questionably operable tumors;
• irradiation with delayed selective surgery.

When irradiating the zones of clinical and subclinical tumor distribution before operative intervention, first of all, the lethal damage of the most highly malignant proliferating cells is achieved, most of which is located in the well-oxygenated peripheral areas of the tumor, in the areas of its growth both in the primary and metastases. Lethal and sublethal injuries also produce non-replicating complexes of cancer cells, thereby reducing their ability to engraft in case of injury to the wound, blood and lymphatic vessels. The death of tumor cells as a result of ionizing effects leads to a decrease in the size of the tumor, delimiting it from surrounding normal tissues due to growth of connective tissue elements.

These changes in tumors are realized only when the optimal focal dose of radiation is used in the preoperative period:

• the dose should be sufficient to cause the death of most of the tumor cells;
• should not cause noticeable changes in normal tissues, leading to disruption of healing of postoperative wounds and an increase in postoperative mortality.

Currently, two methods of pre-operative remote irradiation are most often used:

• daily irradiation of the primary tumor and regional zones in a dose of 2 Gy to a total focal dose of 40 to 45 Gy for 4 to 4.5 weeks of treatment;
• irradiation of similar volumes in a dose of 4 - 5 Gy for 4 - 5 days to a total focal dose of 20 - 25 Gy.

In the case of applying the first technique, the operation is usually performed 2 to 3 weeks after the end of irradiation, and when using the latter, after 1 to 3 days. The latter method can be recommended only for the treatment of patients with operable malignant tumors.

Postoperative radiotherapy for cancer

Assign it for the following purposes:

• "Sterilization" of the operating field from malignant cells and their complexes scattered during surgery;
• complete removal of the remaining malignant tissues after incomplete removal of the tumor and metastases.

Postoperative radiotherapy for cancer is usually done with breast cancer, esophagus, thyroid, uterus, fallopian tubes, vulva, ovaries, kidney, bladder, skin and lips, with more common forms of cancer of the head and neck, salivary glands, cancer direct and large intestine, tumors of endocrine organs. Although many of these tumors are not radiosensitive, this type of treatment can destroy the remnants of the tumor after surgery. At present, the use of organ-preserving surgeries is expanding, especially in breast, salivary gland and rectum cancer, and radical postoperative ionizing treatment is required.

Treatment is advisable to begin no earlier than 2 to 3 weeks after surgery, i.e. After the healing of the wound and the abatement of inflammatory changes in normal tissues.

To achieve the therapeutic effect, it is necessary to give high doses - at least 50-60 Gy, and the focal dose to the area of the unsuccessful tumor or metastases should be increased to 65 - 70 Gy.

In the postoperative period, it is necessary to irradiate the regions of regional tumor metastasis in which no surgical intervention was performed (for example, supraclavicular and parasternal lymph nodes in breast cancer, iliac and paraaortic nodes in uterine cancer, para-aortic nodes in testicular seminaloma). Doses of radiation can be in the range of 45 - 50 Gy. To maintain normal tissues, irradiation after surgery should be performed using the method of classical dose fractionation - 2 Gy per day or medium fractions (3.0-3.5 Gy) with the addition of a daily dose of 2 to 3 fractions with an interval between them of 4 to 5 hours .

Intraoperative radiotherapy for cancer

In recent years, there has been a renewed interest in the use of a remote megavoltage and interstitial irradiation of a tumor or its bed. The advantages of this variant of irradiation are the possibility of visualizing the tumor and the irradiation field, removing normal tissues from the zone of irradiation, and realizing the features of the physical distribution of fast electrons in tissues.

This radiation therapy for cancer is used for the following purposes:

• irradiation of the tumor before its removal;
• irradiation of the tumor bed after radical surgery or irradiation of residual tumor tissue after a non-radical operation;
• irradiation of an unresectable tumor.

A single dose of radiation to the area of the tumor bed or surgical wound is 15 - 20 Gy (dose 13 + 1 Gy is equivalent to a dose of 40 Gy, administered 5 times a week at 2 Gy), which does not affect the course of the postoperative period and causes the death of the majority of subclinical metastases and radiosensitive tumor cells that can be disseminated during surgery.

With radical treatment, the main task is to completely destroy the tumor and cure the disease. Radical radiation therapy for cancer consists of a therapeutic ionizing effect on the area of clinical spread of the tumor and preventive exposure of the zones of possible subclinical damage. Radiation therapy for cancer, carried out mainly for a radical purpose, is used in the following cases:

• mammary cancer;
• cancer of the mouth and lips, pharynx, larynx;
• cancer of female genital organs;
• skin cancer;
• lymphomas;
• primary brain tumors;
• prostate cancer;
• unresectable sarcomas.

Complete removal of the tumor is most often possible in the early stages of the disease, with a small tumor size with high radiosensitivity, without metastases or with single metastases to the nearest regional lymph nodes.

Palliative radiotherapy in cancer is used to minimize the biological activity, inhibit growth, reduce the size of the tumor.

Radiation therapy for cancer, carried out mainly for palliative purposes, is used in the following cases:

• metastases in the bone and the brain;
• chronic bleeding;
• esophageal carcinoma;
• lung cancer;
• to reduce increased intracranial pressure.

At the same time, severe clinical symptoms decrease.

1. Pain (pain in the bones with metastases of breast cancer, bronchus or prostate gland is well suited to short courses).
2. Obstruction (with stenosis of the esophagus, lung atelectasis or compression of the superior vena cava, lung cancer, compression of the ureter in cervical cancer or bladder, palliative radiation therapy often gives a positive effect).
3. Bleeding (causes great anxiety and is usually observed with a common cancer of the cervix and the body of the uterus, bladder, pharynx, bronchi and mouth).
4. Ulceration (radiotherapy can reduce ulceration on the chest wall with breast cancer, perineal cancer in rectal cancer, eliminate the unpleasant odor and thus improve the quality of life).
5. Pathological fracture (irradiation of large foci in the supporting bones of both metastatic nature and primary in sarcoma Ewing and myeloma can prevent fracture, in the presence of fracture treatment should be preceded by fixation of the affected bone).
6. Relief of neurological disorders (metastasis of breast cancer in retrobulbar fiber or retina regress under the influence of this type of treatment, which usually also preserves vision).
7. Relief of systemic symptoms (myasthenia gravis caused by a thymus tumor, responds well to irradiation of the gland).

When radiotherapy for cancer is contraindicated?

Radiation therapy for cancer is not performed in case of severe general condition of the patient, anemia (hemoglobin below 40%), leukopenia (less than 3 109 / l), thrombocytopenia (less than 109 / l), cachexia, intercurrent illness accompanied by fever. Contraindicated radiation therapy in cancer with active pulmonary tuberculosis, acute myocardial infarction, acute and chronic hepatic and renal failure, pregnancy, severe reactions. Because of the danger of bleeding or perforation, this type of treatment is not performed with decaying tumors; Do not appoint with multiple metastases, serous effusions in the cavity and pronounced inflammatory reactions.

Radiation therapy for cancer can be accompanied by the emergence of both forced, unavoidable or permissible, and unacceptable unexpected changes in healthy organs and tissues. At the heart of these changes is the damage to cells, organs, tissues and body systems, the extent of which mainly depends on the size of the dose.

Damages to the severity of the current and the time of their arrest are divided into reactions and complications.

Reactions are changes that occur in organs and tissues at the end of the course, either alone or under the influence of appropriate treatment. They can be local and common.

Complications - persistent, hard-to-eliminate or permanent disorders, caused by tissue necrosis and replacement of their connective tissue, do not pass by themselves, require long-term treatment.