Radiation therapy for cancer

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

Radiation therapy for 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, the treatment can be radical or palliative.

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What is radiation therapy for cancer?

The use of ionizing radiation for the treatment of malignant neoplasms is based on the damaging effect on cells and tissues, leading to their death when receiving appropriate doses.

Radiation cell death is primarily associated with damage to the DNA nucleus, deoxynucleoproteins and DNA membrane complex, gross disturbances in the properties of proteins, cytoplasm, and enzymes. Thus, disturbances occur in all links of metabolic processes in irradiated cancer cells. Morphologically, changes in malignant neoplasms can be represented by three successive 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 some time has passed since its completion.

Radiosensitivity is an internal property of malignant cells. All human organs and tissues are sensitive to ionizing radiation, but their sensitivity is not the same, it changes depending on the state of the body and the action of external factors. The most sensitive to radiation are hematopoietic tissue, the glandular apparatus of the intestine, the epithelium of the sex glands, skin and the lens bag of the eye. Further in terms of radiosensitivity are the endothelium, fibrous tissue, parenchyma of internal organs, cartilaginous tissue, muscles, and nervous tissue. Some of the neoplasms are listed in order of decreasing radiosensitivity:

• seminoma;
• lymphocytic lymphoma;
• other lymphomas, leukemia, myeloma;
• some embryonal sarcomas, small cell lung cancer, choriocarcinoma;
• Ewing's sarcoma;
• squamous cell carcinoma: highly differentiated, moderately differentiated;
• 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 neoplasm originated. Histological structure is an indicative sign for predicting radiosensitivity. Radiosensitivity is affected by the nature of growth, size and duration of its existence. Radiosensitivity of cells at different stages of the cell cycle is not the same. Cells in the mitosis phase have the highest sensitivity. The greatest resistance is in the synthesis phase. The most radiosensitive neoplasms originate from tissue characterized by a high rate of cell division, with a low degree of cell differentiation, exophytic growth and well oxygenated. Highly differentiated, large, long-existing tumors with a large number of anoxic cells resistant to radiation are more resistant to ionizing effects.

To determine the amount of absorbed energy, the concept of radiation dose was introduced. Dose is understood as the amount of energy absorbed per unit mass of irradiated substance. Currently, in accordance with the International System of Units (SI), the absorbed dose is measured in grays (Gy). A single dose is the amount of energy absorbed during one irradiation. A tolerant (tolerable) dose level, or tolerant dose, is a dose at which the frequency of late complications does not exceed 5%. The tolerant (total) dose depends on the irradiation mode and the volume of irradiated tissue. For connective tissue, this value is taken to be 60 Gy with an irradiation area of 100 cm2 ^with daily irradiation of 2 Gy. The biological effect of radiation is determined not only by the value of the total dose, but also by the time during which it is absorbed.

How is radiation therapy performed for cancer?

Radiation therapy for cancer is divided into two main groups: external beam methods and contact irradiation methods.

1. External beam radiation therapy for cancer:
   • static - through open fields, through a lead grid, through a lead wedge filter, through lead screening blocks;
   • movable - rotary, pendulum, tangential, rotary-convergent, rotary 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 for cancer is a combination of one of the methods of external and contact irradiation.
4. Combined methods of treatment of malignant neoplasms:
   • radiation therapy for cancer and surgery;
   • radiation therapy for cancer and chemotherapy, hormone therapy.

Radiation therapy for cancer and its effectiveness can be increased by increasing the tumor's radiosensitivity and weakening the reactions of normal tissues. The differences in the radiosensitivity of tumors and normal tissues are called the radiotherapeutic interval (the higher the therapeutic interval, the greater the dose of radiation that can be delivered to the tumor). To increase the latter, there are several ways of selectively managing tissue radiosensitivity.

• Variations in dose, rhythm and timing of irradiation.
• The use of the radiomodifying effect of oxygen - by selectively increasing the radiosensitivity of the neoplasm by its oxygenation and by reducing the radiosensitivity of normal tissues by creating short-term hypoxia in them.
• Radiosensitization of tumors using certain chemotherapy drugs.

Many antitumor drugs act on dividing cells in a certain phase of the cell cycle. In addition to the direct toxic effect on DNA, they slow down the reparation processes and delay the passage of a cell through a particular phase. In the mitosis phase, which is most sensitive to radiation, the cell is delayed by vinca alkaloids and taxanes. Hydroxyurea inhibits the cycle in the G1 phase, which is more sensitive to this type of treatment compared to the synthesis phase, and 5-fluorouracil inhibits the S phase. As a result, a greater number of cells enter the mitosis phase at the same time, and due to this, the damaging effect of radioactive radiation increases. Drugs such as platinum, when combined with ionizing radiation, inhibit the processes of restoring damage to malignant cells.

• Selective local hyperthermia of the tumor causes a disruption of post-radiation recovery processes. The combination of radioactive irradiation with hyperthermia improves treatment results compared to the independent impact of each of these methods on the tumor. This combination is used in the treatment of patients with melanoma, rectal cancer, breast cancer, head and neck tumors, bone and soft tissue sarcomas.
• Creation of short-term artificial hyperglycemia. A decrease in pH in tumor cells leads to an increase in their radiosensitivity due to the disruption of post-radiation recovery processes in an acidic environment. 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 treatment method as radiation therapy for cancer.

In oncological 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 chemotherapy, immunotherapy, surgical and hormonal treatment).

Radiation therapy for cancer, alone or in combination with chemotherapy, is most often used for cancer in the following locations:

• cervix;
• leather;
• larynx;
• upper 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, a distinction is made between pre-, post- and intraoperative treatment methods.

Preoperative radiation therapy for cancer

Depending on the purposes for which it is prescribed, there are three main forms:

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

When irradiating the zones of clinical and subclinical tumor spread before surgery, lethal damage is primarily achieved to the most highly malignant proliferating cells, most of which are located in well-oxygenated peripheral areas of the neoplasm, in its growth zones both in the primary focus and metastases. Lethal and sublethal damage is also received by non-reproducing complexes of cancer cells, due to which their ability to engraft in the event of penetration into a wound, blood and lymphatic vessels is reduced. The death of tumor cells as a result of ionizing exposure leads to a decrease in the size of the tumor, its delimitation from the surrounding normal tissues due to the proliferation of connective tissue elements.

The indicated changes in tumors are realized only when using the optimal focal dose of radiation in the preoperative period:

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

Currently, two methods of preoperative external beam irradiation are most commonly used:

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

In the case of the first method, the operation is usually performed 2-3 weeks after the end of irradiation, and in the case of the second method, 1-3 days later. The latter method can only be recommended for the treatment of patients with operable malignant tumors.

Postoperative radiation therapy for cancer

It is prescribed for the following purposes:

• “sterilization” of the surgical field from malignant cells and their complexes scattered during the surgical intervention;
• complete removal of remaining malignant tissue after incomplete removal of the tumor and metastases.

Postoperative radiation therapy for cancer is commonly used for cancers of the breast, esophagus, thyroid, uterus, fallopian tubes, vulva, ovary, kidney, bladder, skin, and lip, and for more common head and neck cancers, salivary gland tumors, colorectal cancer, and endocrine tumors. Although many of these tumors are not radiosensitive, this type of treatment can destroy any remaining tumor after surgery. Organ-preserving surgery is increasingly used, especially for breast, salivary gland, and rectal cancers, which require radical postoperative ionizing therapy.

It is advisable to begin treatment no earlier than 2-3 weeks after surgery, i.e. after the wound has healed and inflammatory changes in normal tissues have subsided.

To achieve a therapeutic effect, it is necessary to administer high doses - at least 50 - 60 Gy, and it is advisable to increase the focal dose to the area of the unremoved tumor or metastases to 65 - 70 Gy.

In the postoperative period, it is necessary to irradiate the areas of regional tumor metastasis, where surgery was not performed (for example, supraclavicular and parasternal lymph nodes in breast cancer, iliac and paraaortic nodes in uterine cancer, paraaortic nodes in testicular seminoma). Radiation doses can be within 45-50 Gy. To preserve normal tissues, irradiation after surgery should be performed using the classical dose fractionation method - 2 Gy per day or in medium fractions (3.0-3.5 Gy) with the addition of a daily dose in 2-3 fractions with an interval of 4-5 hours between them.

Intraoperative radiation therapy for cancer

In recent years, interest in the use of remote megavoltage and intra-tissue irradiation of a tumor or its bed has increased again. The advantages of this irradiation option include the ability to visualize the tumor and the irradiation field, remove normal tissues from the irradiation zone, and implement 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 non-radical surgery;
• irradiation of an unresectable tumor.

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

In radical treatment, the main goal is to completely destroy the tumor and cure the disease. Radical radiation therapy for cancer consists of therapeutic ionizing effects on the zone of clinical spread of the tumor and prophylactic irradiation of zones of possible subclinical damage. Radiation therapy for cancer, carried out mainly for a radical purpose, is used in the following cases:

• breast cancer;
• cancer of the oral cavity and lips, pharynx, larynx;
• cancer of the 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 small tumor sizes and high radiosensitivity, without metastases or with single metastases in the nearest regional lymph nodes.

Palliative radiation therapy for cancer is used to maximally reduce biological activity, inhibit growth, and reduce the size of the tumor.

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

• metastases to bones and brain;
• chronic bleeding;
• esophageal cancer;
• lung cancer;
• to reduce increased intracranial pressure.

At the same time, severe clinical symptoms are reduced.

1. Pain (bone pain due to metastases from breast, bronchial or prostate cancer responds well to short courses).
2. Obstruction (in cases of esophageal stenosis, pulmonary atelectasis or compression of the superior vena cava, lung cancer, compression of the ureter in cervical or bladder cancer, palliative radiotherapy often has a positive effect).
3. Bleeding (causes great concern and is usually observed in advanced cancer of the cervix and body of the uterus, bladder, pharynx, bronchi and oral cavity).
4. Ulceration (radiation therapy can reduce ulceration on the chest wall in breast cancer, on the perineum in rectal cancer, eliminate unpleasant odor and thus improve quality of life).
5. Pathological fracture (irradiation of large foci in supporting bones, both metastatic and primary in Ewing's sarcoma and myeloma, can prevent fracture; if a fracture is present, treatment should be preceded by fixation of the affected bone).
6. Alleviation of neurological disorders (metastases of breast cancer to the retrobulbar tissue or retina regress under the influence of this type of treatment, which usually also preserves vision).
7. Relief of systemic symptoms (myasthenia gravis due to a tumor of the thymus gland responds well to irradiation of the gland).

When is radiation therapy contraindicated for cancer?

Radiation therapy for cancer is not performed in severe general condition of the patient, anemia (hemoglobin below 40%), leukopenia (less than 3-109/l), thrombocytopenia (less than 109/l), cachexia, intercurrent diseases accompanied by a fever. Radiation therapy for cancer is contraindicated in active pulmonary tuberculosis, acute myocardial infarction, acute and chronic liver and kidney failure, pregnancy, severe reactions. Due to the risk of bleeding or perforation, this type of treatment is not performed for disintegrating tumors; it is not prescribed for multiple metastases, serous effusions in the cavity and severe inflammatory reactions.

Radiation therapy for cancer may be accompanied by the occurrence of both forced, inevitable or acceptable, and unacceptable unexpected changes in healthy organs and tissues. These changes are based on damage to cells, organs, tissues and body systems, the extent of which mainly depends on the dose.

Depending on the severity of the course and the time it takes to resolve, injuries are divided into reactions and complications.

Reactions are changes that occur in organs and tissues at the end of the course, passing on their own or under the influence of appropriate treatment. They can be local and general.

Complications are persistent, difficult to eliminate or permanent disorders caused by tissue necrosis and their replacement with connective tissue, do not go away on their own, and require long-term treatment.