Foundations of

Radiotherapy (RT)

Radiotherapy

➢Radiotherapy is a science about use of

ionizing radiation (IR) mainly to treat

malignant tumors.

➢ The first time of using X-rays was in 1896.

Clinicobiologic foundations of RT of Tumors

The therapeutic use of irradiations is

based on their biological action - their

ability to cause changes in cells,

tissues, organs, the body as a whole.

It depends on the ABSORBED DOSE (AD)

– energy transmitted to irradiated

tissues (Gr).

The main principles of radiotherapy for malignant tumors.

➢ The timely application of radiotherapy at the early stages of the disease.

➢ The choice of the most rational methods of irradiation.

➢ Holding up an optimal dose at an optimal time to the tumor while saving the viability of surrounding healthy tissues and under the decrease of the total dose absorbed by the organism.

➢ Simultaneous radiation influence on the primary tumor and regional metastasizing ways.

➢ The complexness of the patient’s treatment: the application, together with radiotherapy, means which increase the general and local reactivity of the organism.

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➢ The main principles of radiotherapy for non-neoplastic lesions.

● Radiotherapy for non-neoplastic lesions is only used when well-grounded indications for that are present.

● Radiotherapy is the method of choice and it is used, as a rule, when a positive effect of already applied medications has not been achieved, and a probability of somatic, genetic and radiation damages is excluded completely.

● Radiotherapy for non-neoplastic lesions should not be applied to children, teenagers and pregnant women.

● The main method of irradiation is an immediate influence on the pathologically changed organs and tissues.

● Radiotherapy should be conducted with the application of methods which minimize the irradiation of vitally important organs and tissues.

The sources of ionizing radiations applied for radiotherapy.

● Radionuclide sources of ionizing radiations – are sources of an immediate effect radiations containing radioactive substances.

➢ A closed source of ionizing radiations – is a radionuclide source of ionizing radiations the construction of which excludes getting of the radioactive substance (it contains) to the environment ( for example, radioactive needles, gamma therapeutic apparatuses for static and dynamic irradiation).

➢ An open source of ionizing radiations – is a radionuclide source of ionizing radiations whose application makes getting of the radioactive substance (it contains) to the environment possible (solutions and suspensions of RP).

● Non-radionuclide sources of ionizing radiations – are technical devices not containing radioactive substances but under certain circumstances are capable of generating ionizing radiations at the expense of accelerating and decelerating charged particles (for example, linear accelerators of electrons, X-ray apparatuses for close-focus and long-focus X-ray therapy, betatrons).

Depending on the spatial location of the radiation source in relation to the patient’s body, they perform external irradiation (on the skin’s side) and internal irradiation (the radiation source is placed in the patient’s body).

Programs of radiotherapy.

Depending on the treatment purpose, they distinguish:

➢ The radical program of radiotherapy supposes the complete destruction of tumorous elements in the zone of the primary focus and is aimed at the full recovery of the patient. They irradiate the primary focus and zones of regional metastasizing. The total dose per part of the primary tumor is, as a rule, 60-75 Gy, on the zones of metastazing – 45-50 Gy.

➢ The palliative program of radiotherapy is performed for patients with the advanced tumorous process under which it is impossible to achieve a complete and stable recovery. As a result of radiotherapy there comes just tumors’ partial regression, intoxication decreases, the pain syndrome disappears and the function of the organ damaged by a tumor is partially restored, which provides the patient’s lifetime prolongation. Under palliative radiotherapy they use the total doses of 40-55 Gy.

➢ The symptomatic program of radiotherapy is applied for removing the severest symptoms of tumor disease (the pain syndrome, compression of the ureters, bile ducts, obturation of the esophagus lumen).

The doses of radiations applied for treating malignant tumors.

The following concepts are distinguished:

➢ A single focal dose (SFD) – the dose which is held up to the pathological area for one session of irradiation.

➢ A total focal dose (TFD) - the dose which is held up to the pathological area during the whole course of treatment.

➢ A single skin dose (SSD) - the dose which is held up to the skin field for one session of irradiation.

➢ A total skin dose (TSD) - the dose which is held up to the skin field during the whole course of treatment.

Depending on the tumor’s histological structure, its radiosensitivity, size and depth of location, they apply the following total focal doses (TFD) for a treatment course:

➢ For the destruction of epithelial tumors – TFD 50-70 Gy.

➢ For the destruction of adenocarcinomas – TFD 70-80 Gy.

➢ For the destruction of sarcomas of muscular and osteogeneous origin and melanomas – TFD 80-90 Gy.

To prevent tissues radiation damage, total doses of radiation are divided into some parts – fractions.

The radiation rhythm or fractioning regimen- the timing of the dose absorption.

Small fractioning – 2 Gr 5 times a week –

for tumors with high & moderate radiosensitivity.

Average fractioning - 3-4 Gr 3-4 times a week

for resistant tumors.

Large fractioning – 4 Gr & more (10 Gr). It depends on the tactics of treatment.

The uninterrupted regimen lasts for days & weeks.

Radiation reactions.➢

Radiation reactions – are reversible changes in tissues which pass in 2-3 weeks after irradiation without any special treatment.

Local radiation reactions:

1.Radiation erythema:

➢ emerges after gamma irradiation on the skin field by tiny fractions: SFD 2 Gy up to TFD 30-35 Gy.

➢ is characterized by the stable reddening of the skin, edema, tenderness.

➢ disappears in 2-4 weeks after ceasing the treatment.

2.Dry radiodermitis:

● appears under gamma irradiation on the skin field by tiny fractions: SFD 2 Gy up to TFD 40-50 Gy.

● objectively: there are augmented erythema and edema, dermis cell division stops as well as that of the hair follicles, there emerges epilation and desquamation of superficial tissues, the epidermis exfoliates, the skin becomes dry and pigmented.

3.Exudative (wet) radiodermitis:

➢ emerges under gamma irradiation on the skin field by tiny fractions up to TFD 50-60 Gy.

➢ the epidermis is desquamated, on the edges of the desquamated surface there appears a strip of new epidermis which gradually, within 2-3 weeks, spreads over up to the centre of the damaged area of the skin.

➢ the skin in the damaged area exfoliates for a long time, is unevenly pigmented, in remote terms there occurs atrophy of epidermis and epilation.

➢ For the sake of prophylaxis of skin radiation reactions, it is recommended to smear the irradiation fields with indifferent fats.

➢ It is strictly forbidden to smear the skin with ointments containing salts of metals for prophylaxis of skin radiation burns!

Radiation damages.

Radiation damages – are profound, often irreversible, changes of organs and tissues which need a special treatment.

➢ Early radiation damages can develop during irradiation or within 3 months after irradiation under exceeding tolerant levels of tissues irradiation. They are characteristic of more radiosensitive and well regenerating tissues, that is why such damages are quickly recovered.

Radiation skin necrosis is not recovered on its own, it can get malign. For the prophylaxis of skin damages under tiny and medium fractioning they consider the concept of a tolerant skin dose.

A tolerant skin dose is the total maximal skin dose of ionizing radiation under the exceeding of which there emerge radiation skin damages. It is obligatorily taken into account while making up the plan of the patients radiation treatment.

➢ Late radiation damages develop 3 months (sometimes several years) later after irradiation with doses exceeding tolerant levels of skin irradiation.

To late radiation damages belong local (radiation fibrosis, indurative edema, radiation ulcer, radiation cancer; radiation damages of internal organs – radiation fibrosis, radiation necrosis, radiation ulcer) and general radiation damages (stable changes in the blood, CNS, esophagus, endocrine glands, chronic radiation disease).

Radiation damages of tissues require surgical treatment, hormonotherapy, etc. For that reason, to prevent radiation damages of tissues and organs one has to keep strictly to the methods and standarts of radiotherapy.

Dosimetric and topometric preparation.

➢ Various sources and methods of radiation therapy enable to irradiate with a necessary therapeutic dose pathologic processes that are located at different depth. The penetrating capacity of ionizing radiation into the human body depends on the type and energy of irradiations. The relation of the dose at the given depth to the dose in the skin is called a relative or percentage depth dose.

➢ On the manufactured section of the patient’s body with the place of the pathological area marked on it, a radiotherapist together with a physicist-dosimetrist design the program of irradiation, determine the volume of the irradiation zone.

➢ They choose the type of radiation and method of irradiation, sizes and shape of the irradiation fields, direction of the ray beams and draw them on the topographic-anatomic sketch. The topographic-anatomic sketch is performed nowadays on the transversal CT or MRI section at the level of the tumor centre. After the irradiation fields have been drawn, they put perpendicular lines through the appointed fields’ centres which cross in the tumor centre.

➢ They define the percent depth dose in the damage focus of each irradiation field. The number of irradiation fields is determined considering the account of the irradiated tissues tolerance level.

➢ The value of the radiation dose which is held up to the tumor from each irradiation field is limited by normal tissues’ tolerance. A tolerant dose is the threshold dose of ionizing radiation which does not cause irreversible tissue changes. Exceeding tolerant doses can lead to normal tissues’ damages, to the decrease of their regeneratory capacity, which can affect negatively the disease state.

Radiotherapeutic interval.

➢ Radiotherapeutic interval – is the difference between the degree of damage and the degree of recovery of tumor and healthy tissues under equal doses absorbed by them.

➢ To increase the effectiveness of radiotherapy and decrease of the negative impact of ionizing radiation on surrounding healthy tissues, they apply radiomodifiers.

➢ Radiomodifiers applied for increasing tumor cell radiosensitivity are called radiosensibilizers (for example, saturating tumors with oxygen, hyperthermia, magnetotherapy, pharmatheutical preparations and hemopreparations – fluorouracil, ftoraful, methotrexat).

➢ Radiomodifiers decreasing the radiosensitivity of normal tissues are called radioprotectors (for example, pharmatheutical preparations (cystamine, serotonin, etiol); a decrease of the oxygen partial pressure, hypothermia).

In 1938, B.Ye. Peterson, on the basis of tumors’ radiosensitivity research, developed the radiosensitivity classification:

➢ Radiosensitive tumors – lymphosarcoma, lymphogranulomatosis, reticulosarcoma, basal-cell cancer, seminoma, timoma, Ewing’s tumor and others.

➢ Moderately radiosensitive tumors – planocellular cancer with different degrees of differentiation.

➢ Moderately radioresistant tumors – adenocarcinoma.

➢ Radioresistant tumors – neurofibrosarcoma, osteogenic sarcoma, fibrochondrosarcoma, skin melanoma and others.

Tumors radiosensitivity depends on:

➢ their histologic structure;

➢ the degree of cellular elements differentiation;

➢ phase of the mitotic cycle (in the phase of mitoses tumor cells are most radiosensitive);

➢ the stroma-parenchyma relationship (tumors rich in stroma are less sensitive to radiation impact as a consequence of their poor oxygenation);

➢ blood supply (tumors with sufficient blood supply are more radiosensitive as a consequence of the greater oxygen partial pressure values in them at the account of “the oxygenic effect”;

➢ localization, tumor’s size (tiny tumors are more sensitive than large ones);

➢ speed of growth (cells with high growth rate are more radiosensitive than those with low growth rate;

➢ nature of growth (exophytic tumors are more radiosensitive than endophytic types).

The strategy of a radiotherapy course.

A radiotherapy course – is the period of radiation treatment during which the patient receives a total focal dose. Making a plan of radiotherapy is performed by three experts (a radiotherapist, a medical physicist and a roentgenologist) for each individual patient according to the existing strategy of radiotherapy.

A radiotherapy course is comprised of three periods:

1. The preradiation period:

➢ A detailed examination of a patient (clinical, laboratory, US, X-ray, CT, MRI and other studies).

➢ Finding out the histological form of the disease (morphological or histological verification).

➢ Finding out the indications for radiotherapy.

➢ Excluding contraindications for radiotherapy.

➢ Choosing the type and method of radiotherapy and additional non-radiation medication measures.

➢ Finding out the topographic-anatomic relationship of the tumor and surrounding healthy organs and tissues (topometric preparation of a patient).

➢ The choice of the optimal single and total dose of radiation.

➢ The choice of the optimal regime of irradiation (single, fractionated, continuous).

➢ The technology of irradiation.

2. The radiation period:

➢ Performing irradiation

➢ The application of treatment additional methods.

➢ Taking care of patients, in case of need – correction in treatment planning.

➢ Monitoring possible local radiation reactions.

3. The postadiation period:

➢ Following up the patient’s state.

➢ Evaluating the treatment effectiveness.

➢ Monitoring possible local radiation reactions and damages.

➢ Dispansery monitoring the patient twice a year. If there is no relapse in 10 years, the patient is excluded out of the oncological list.

The factors influencing

the effectiveness of radiotherapy.

➢The tissue irradiation volume.

➢The radiation type.

➢The irradiation time and fractioning.

The indications for radiotherapy

of malignant tumors.

➢ Malignant tumors.

➢ Metastatic injuries.

➢ Some relapsing benign tumors (for example, the brain tumors).

➢ Hemoblastoses: Hodgkin’s disease, non-Hodgkin’s malignant

lymphomas, multiple myeloma.

The contraindications for radiotherapy of malignant tumors.

● The absolute contraindications:

➢ Decompensation of function of the cardiovascular system, liver and kidney functions.

➢ Decompensated forms of diabetes.

➢ An expressed intoxication, rise of body temperature above 38°C.

➢ The presence of anemia (Hb < 70 g/l), leucopenia (L < 3*109/l), thrombocytopenia (Thr < 150*109/l).

➢ Cancer cachexia, disintegration of tumors with hemorrhage, multiple remote metastases.

➢ Survived myocardial infarction (less than 5-6 months since the coming of IM).

➢ Active tuberculosis.

➢ Phychic diseases (in which no contact with the patient is possible and motor hyperactivity is increased).

● The relative contraindications:

➢ The absence of a clear pathomorphological analysis.

➢ Acute infectious diseases or exacerbation of chronic infectious diseases.

➢ Early radiation reactions emerging during the radiotherapy course (radiotherapy is going on after their liquidation).

➢ A decrease in peripheric blood indices during radiotherapy down to Hb < 70 g/l, L < 3*109/l, Thr < 150*109/l. With the normalization of these indices the radiotherapy course continuation is possible.

➢ Infancy (childhood), pregnancy and lactation period (prescribing radiotherapy is possible in malignant tumors).

The indications for radiotherapy of non-neoplastic lesions.

➢ Skin basal-cell cancer.

➢ Diseases of the nervous system – radiculites, neuritis, syringomyelia, postamputation pain syndrome, etc.

➢ Inflammatory diseases – furuncules, carbuncules, mastites, thrombophlebitis, periproctitis, etc.

➢ Degenerative-dystrophic and metabolic processes – arthroses, spondyloses, osteochondroses, etc.

➢ Skin disease – dermatoses, non-microbial eczema.

➢ Postoperative complications – anastomosites, fistulas, etc.

The containdications for radiotherapy

of non-neoplastic lesions.

● The absolute contraindications:

➢ A patient’s severe state.

➢ Decompensated states of the cardiovascular and respiratory systems, liver and kidneys.

➢ Anemia (Hb < 70 g/l), leucopenia (L < 3*109/l), thrombocytopenia (Thr < 150*109/l).

➢ Radiation disease and radiation damages (survived in the past).

➢ Infancy (childhood).

➢ Pregnancy.

● The relative contraindications:

➢ Acute septic and infectious diseases.

➢ Expressed spread skin diseases and inflammatory skin processes.

Types and methods of radiotherapy:

At the basis of the radiation types classification there is laid their division after a type of ionizing radiation: X-ray therapy, gamma-therapy, beta-therapy, megavoltage therapy, proton therapy, neutron therapy.

The classification of radiotherapy methods:

1. Long-focus (source-skin distance (SSD) is within the interval of 30 cm to 2 m.• X-ray therapy (superficial, half-deep, deep).

• gamma-therapy (static, dynamic).

• irradiation with high energy sources (with the application of linear or cyclic accelerators).

2. Close-focus (SSD is within the interval of 1,5 cm to 30 cm) – X-ray therapy.

3. Contact (SSD is 0 cm)

➢ application.

➢ interstitial.

➢ intracavitary.

➢ with incorporated radionuclides.

4. Radiosurgery.

Each of the above mentioned methods of the treating malignant tumors can be applied as:

➢ the independent method – long-focus or close-focus therapy;

➢ the united method of radiotherapy – a combination of the long-focus and close-focus methods of irradiation;

➢ the combined method of treating malignant tumors includes radiotherapy and surgical treatment under which preoperative, suboperative and postoperative irradiation can be applied.

➢ the complex method of treating malignant tumors presupposes the application of radiotherapy methods together with hormonotherapy and chemotherapy in the treatment.

X-ray therapy.

X-ray therapy is a type of radiotherapy in which X-radiation is used for medical purposes.

Methods of X-ray therapy.

1. Long-focus X-ray therapy – is performed with the help of the RUM-17 X-ray apparatus.

Depending on the depth of the pathology in relation to the skin surface, long-focus X-ray therapy with the help of the RUM-17 apparatus is divided into:

➢ Superficial – used for irradiating the damaged area at the depth of up to 1 cm from the skin surface.

➢ Half-deep – used for irradiating the damaged area at the depth of up to 3 cm from the skin surface.

➢ Deep - used for irradiating the damaged area at the depth of up to 5 cm from the skin surface.

2. Close-focus X-ray therapy – is used in the localization of the pathology at the depth of up to 1 cm from the skin surface. In close-focus X-ray therapy they more often use aluminium filters of 0,1-3 mm and cones of various shapes and sizes.

To close-focus X-ray therapy there is also referred therapy with ultrasoft X-rays – Bucky rayswhich are generated at the voltage of 10-25 kV. The penetrating capacity of Bucky rays in the skin and mucous membranes does not exceed 1,5 mm.

They are used for the treatment of superficially located inflammatory processes, for example, in eczema and dermatitis of the scrotum and the mammary gland nipple, in blepharites and others.

Long-focus radiotherapy.

Long-focus radiotherapy is performed with the help of gamma-therapeutic apparatuses, generators of decelerating high energy radiation and generators of high energy corpuscular radiations (synchrophasotron, synchrocyclotron and others).

Types of a long-focus gamma-therapy.

Depending on the dose distribution in the space they distinguish:

● Static distant gamma-therapy – is performed with open fields (unifield, byfield and multifield irradiations). Under static irradiation the radiation source during the whole time of treatment remains in a fixed position in relation to the patient.

● Dynamic distant gamma-therapy – is characterized by the relocation of the radiation source in relation to the patient during irradiation. There are exist rotation, pendulum-like (sector), tangent (eccentric), rotation-convergent gamma-therapy with managed speed.

The advantages of mobile irradiation over static one are the following:

● a high exactitude of the ray beam centration;

● a considerable decrease and even distribution of radiation load on the skin, which enables to hold up higher doses to the pathological area.

Radiotherapy with high energy sources.

1.Electron-photon therapy

– is performed distantly with the use of linear electrons accelerators, betatrons generating electrons and decelerating radiation with the energy within the range of 1 to 45 MeV.

➢ The application of linear accelerators reduces as much as twice the number of neoplasms relapses and radiation reactions as compared to the irradiation on devices with cobalt.

➢ New radiotherapy technologies introduced into practice, for example IGRT (Image Guided Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy) and PVI (Portal Vision Imager) enable to control visually the accuracy of irradiation in the real time regime in the process of performing each treatment session with the help of a kilovolt radiation source connected to a linear accelerator.

➢ It is important to note that the opportunities of the clinic application of the linear accelerator with a multiplate collimator are much wider than those of a gamma and cyberknife. With help of this apparatus one can form irradiation fields sizes from 5*5 mm to 40*40 cm, which extends significantly the range of its application in oncology: there is the possibility to treat foci of any size.

➢ Electron therapy is indicated both in superficially located (skin cancer, the oral cavity mucous membrane, breast cancer relapses) and deeply located (cancer of the lungs, brain, kidneys and others) malignant neoplasms.

2. Neutron therapy– is a type of corpuscular radiotherapy which is performed with help of neutron radiation. In the interaction of neutron radiation with a substance there prevail the processes that lead to ionization with a high linear energy transmission, therefore it is also called densely-ionizing.

➢ For neutron therapy they use neutron generators for irradiation and neutron-generating RP. In neutron therapy they use long-focus, intracavitary and interstitial irradiation.

➢ Neutron therapy is performed with the help of cyclotrons. The peculiarity of the neutron radiation biological effect is the insignificant dependence of the treatment effect on a cellular cycle stage and oxygen partial pressure in the tissues being irradiated. This facilitates the destruction of malignant tumors the radioresistance of which is conditioned by the cells which divide slowly and the cells that are in the state of hypoxia.

➢ To distant irradiation they refer Boron neutron capture therapy. A therapeutic effect emerges as a result of capturing thermal or intermediate neutrons by the nuclei elements previously accumulated in a tumor (for example, 10B) which capture neutrons and disintegrate releasing ɑ-particles creating the high density of ionization. This enables to bring up a significant dose of irradiation to a tumor.

➢ Intracavitary and interstitial neutron therapy (brachytherapy) can be performed with help of the source of mixed neutron and gamma radiation 252Cf (in patients with cervical cancer, tongue cancer and mucous membrane cancer of oral cavity).

3. Proton therapy

➢ – is a type of corpuscular radiation energy based on the application of high-energy protons accelerated on synchrophasotrons and synchrocyclotrons.

➢ Proton therapy is used for irradiating distinctly delimited pathological foci as well as for irradiating deeply located tumors when the irradiation zone is entered by a large volume of healthy tissues.

➢ Proton therapy is applied for irradiating intracranial tumors of small volume (for example, hypophysis adenoma, eye tumors and others). The tumor is irradiated momentarily from many source positions, due to which in the focus there is created a significant radiation dose.

➢ Proton therapy is also applied for the treatment of cervical cancer as well as that of the nasopharynx, prostate gland and others.