Radiotherapy uses ionizing radiation to treat cancer. There are two main types - external beam radiotherapy which uses radiation from outside the body, and brachytherapy which places radioactive sources inside or near the tumor. The radiation damages cancer cell DNA directly or through free radicals, limiting cell division and causing cell death. Different techniques are used depending on the tumor location and size to deliver precise radiation doses while sparing surrounding healthy tissues.

1. Radiotherapy

2. Radiotherapy---TYPES
 Radiotherapy and chemotherapy are the important modalities of therapy
for human cancers apart from surgery
 Primary therapy---radiotherapy in carcinoma cervix and chemotherapy in
gestational trophoblastic neoplasia
 Multidisciplinary approach---- is needed for the treatment of some
malignancies to improve the outcome.
 Palliation approach ---- incapacitating symptoms when cure may not be
achieved.

3. Radiotherapy---Mechanism
 ➢ Radiotherapy is a science about use of ionizing radiation (IR) mainly to
treat malignant tumors.
 It depends on the ABSORBED DOSE (AD) – energy transmitted to
irradiated tissues (Gr).
 ➢ The first time of using X-rays was in 1896.

4. Radiobiology of normal tissues
 The effects of radiation on tissues are generally of two types:
 A. Loss of mature functional cells by apoptosis (programmed cell death). This usually
occurs within 24 hours of radiation.
 B. Loss of cellular reproductive capacity. The severity depends upon the total dose of
radiation, length of time over which radiotherapy is delivered and the radiosensitivity of
the particular cell types. Usually lost cells are replaced by proliferation of surviving stem
cells or progenitor cells.

5. Ionizing radiation
 (i) Electromagnetic radiation--Electromagnetic radiation:This consists of
quanta of energy and wavelength (photon radiation). They are of two
types—X-rays and gamma rays. These electromagnetic waves travel in
discrete bundles called ‘Photons’.
 (ii) Particulate radiation.-- This consists of atomic subparticles such as
electrons, protons and neutrons. Only electrons (β-rays) are used in
radiotherapy

6. Ionizing radiation
 Gamma rays are produced spontaneously as a result of decay of the atomic nucleus of
some radio-active isotopes. 60Cobalt or 192Iridium is a source of γ-rays.
 „X-rays are produced outside the atomic nucleus. When fast-moving electrons approach
the fields around the nuclei of atoms of a target material (tungsten), they are deflected
from their path. The energy thus emitted in the form of electromagnetic radiation
(photons) is X-rays. Machines such as betatron (circular fashion) and linear accelerator
(linear fashion) can accelerate electrons with high kinetic energy. Therefore, X-rays
generated by these machines are very high in energy

9. Radiotherapy -- mechanism
 X-rays and gamma rays are collectively called photons. When photons interact with
matter (tissue), three effects are observed: (i) photoelectric effect, (ii) compton scattering
and (iii) pair production. In human radiation therapy, compton scattering is the major
interaction of photons with tissue .
 X-rays and gamma rays have shorter wavelength and high frequency. They have high
kinetic energy. X-rays and gamma rays possess considerable power of tissue penetration
depending on the photon energy and the density of the matter through which they pass.
The photon energy produced from radioactive cobalt is 1.2 million electron volts (Mev).
External photon beam radiation is usually derived from a linear accelerator

10. Radioactive isotopes used in gynecological malignancies
Element isotope Energy (mev) Half-life clinical use
Cesium 137 (137Cs) 0.514 30 yrs intracavitary implants-
temporary
Radium 236 (236Ra) 3.26 1600 yrs historical
Cobalt 60 (60Co) 1.173 1.173 5.3 yrs
iridium 192 (192ir) 0.38 74.2 days interstitial implant
(temporary)
iodine 125 (125i) 0.028 60.2 days interstitial implant
(permanent)
phosphorus 32 (32p) none 14.3 days intracavitary (permanent)

11. Techniques of radiation therapy
 Brachytherapy---It gives a very high dose of radiation where the source of
radiation is placed within, or close to the tumor. The application may be (i)
Intracavitary (ii) Interstitial or (iii) Surface (skin). Damage to normal tissues
is less as there is rapid falloff of radiation around the source (inverse
square law).
 Intracavitary: The devices for brachytherapy consist of hollow stem
(intrauterine tandem), which is placed within the uterine cavity .Especially
designed devices used for vaginal placements are called vaginal ovoids or
colpostats.

12. Techniques of radiation therapy
 Interstitial form of brachytherapy consists of placement of radioactive
sources (needles, wires or seeds) within the tissues.
 Commonly used sources are Iridium-192 (192Ir), Cesium-137 (137Cs) and
Cobalt 60 (60Co). Small volume of tumor, as in early cases of vaginal
carcinoma, can be treated with the method. Normal tissues are spared
from radiation injury.
 Intraperitoneal instillation is another mode of local therapy--gold or
phosphorus,

13. After loading technique:
 It is a modern development of brachytherapy to prevent radiation
complications to the personnel. A mock insertion of applicators is
performed and an X-ray is taken to note their exact position.
 After loading technique may be manual or by remote control. Later on,
live radioactive sources are introduced by remote control in identical
manner. Remote after loading system uses Selectron (137Cs) or high dose
Selectron (60Co). Remote control systems allow complete protection of
staff from radiation exposure

14. Techniques of radiation therapy
 Brachytherapy can be either low dose rate (LDR) or a high dose rate (HDR) system. LDR
require hospital admission and deliver dose at about 50-100 cGy/hour. HDR systems are
commonly done as outpatient basis. The dose rate delivered is at 100 cGy/minute.
 Advantages: (a) Localized high radiation dose to a small tumor volume with high local
control. Radiation dose in the surrounding normal tissues is less as there is sharp fall-off
according to inverse square law
 Disadvantages: (a) Large tumors are usually unsuitable unless used following EBRT and/or
chemotherapy. (b) Risks of exposure to medical and nursing personnel due to gamma
rays.

15. Brachytherapy technique
 Small radioactive sources, mainly radium sulphate is mixed with some inert powder and
packed in small needles or tubes. These are used for interstitial, intracavitary or surface
applications. Radiation sources for intracavitary radiation are Radium (226Ra), Cesium
(137Cs) or Cobalt (60Co). The container is made up of platinum, gold or alloy steel to
absorb alpha and beta particles and allowing the gamma rays to sterilize the cancer cells.
 In carcinoma cervix, the tandems are inserted in the uterine cavity and the ovoids and
colpostats are placed in the vaginal vault under anesthesia

16. Brachytherapy technique
 In Paris and Manchester techniques, the source strength is smaller but exposure time is increased.
The vaginal source is away from the cervix. They are used with either preloaded or afterloaded
special applicators.
 One treatment period in Paris technique is 96–200 hours as compared to Stockholm technique
where each application is 24–28 hours in duration .
 Manchester system, which is a modification of the Paris technique, delivers constant isodose at
different depths, regardless of the size of the uterus and vagina. In Stockholm technique large high
intensity source with less exposure time is given, but the vaginal source is closer to the cervix

21. Isodose distribution curve with intracavitary
irradiation

22. External Beam Radiotherapy (EBRT)
 EBRT or teletherapy is the treatment with beams of ionizing radiation produced from a
source external to the patient.
 Superficial tumors may be treated with X-rays of low energy in the range of 80-300 KV.
Deeper-seated tumors are usually treated using mega-voltage photons. Cobalt 60 is the
common teletherapy source for EBRT, the other one is cesium 137.
 External radiation therapy is used to treat large volumes (tumor, lymph nodes,
parametrium) .
 It is designed to deliver a uniform radiation dose to the tumor volume without ‘hot’ (excess
dose) or ‘cold’ (under dose) spots. Accurate tumor localization and volume measurement
are essential. Greater the tumor volume, higher the radiation dose required

23. Instillation of Radioisotopes into the
Peritoneal or Pleural Cavity
 Radioactive isotopes of either gold or phosphorus, linked to carrier
colloids, are commonly used in ovarian cancer. This can give radiation only
to a depth of 4-8 mm. Radioactive chromic phosphate (32P) emits pure β-
rays and has got longer half-life (14.3 days) and deeper penetration (8
mm) power compared to radio gold (198Au). Small volume of tumor in the
peritoneal or pleural cavity is treated with solution of radioisotopes.

24. Measurement of Radiation Radiation
absorption dose (Gray)
 is the unit used to measure the amount of energy absorbed per unit mass
of tissue. One gray (Gy) is equivalent to 1 Joule/kg which is equivalent to
100 rads. Currently, the term centigray (cGy) is used.
 One cGy is equivalent to one rad. Amount of radiation the patient
receives is calculated by dosimetry. Homogeneous irradiation of tissues is
desirable . Primary tumor should receive high dose.
 Brachytherapy and teletherapy should be combined to provide adequate
irradiation to the primary tumor as well as the pelvic lymph nodes and the
parametrium

25. Biological effects of radiation (radiobiology)
 (1) Direct action: Where the radiation is absorbed, it causes damage to
DNA directly. This is the predominant mechanism of action of particulate
radiation (neutrons).
 (2) Indirect action: Where the radiation interact with other substances (H2
O) in the cell to produce free radicals (OH– ) which in turn damage the
DNA.
 Radiation, depending on the dose and time of exposure may cause (a)
gene mutation (b) abnormal cell mitosis and (c) derangement of
reproductive ability of the cell—“progeria”.

26. The target for radiation injury is DNA
 Ultimately, there is limited cell mitosis and mitotic cell death. There is
cytoplasmic vacuolation and fragmentation.
 Ionizing radiation also produces damage to nuclear and plasma
membranes. This effect of ionizing radiation is common for both the
normal and neoplastic tissues, encountered in the radiation path.
 Radiation complications are mainly due to interaction with the normal
tissues .When the radiation effect to a cell is sublethal, cellular DNA may
undergo repair and the cell survives. Lethal effect kills the cell.

27. Radiation dose
 According to the “inverse square law” there is reduction of radiation at a
distance from the source in brachytherapy. This protects the normal
tissues

28. Advantages of primary radiotherapy- ca cervix
 Wider applicability in all stages of carcinoma cervix.
 Survival rate 85%, comparable with that of surgery in early stages.
 Less primary mortality and morbidity.
 Individualization of dose distributions/requirement possible.

29. Contraindication of radiotherapy
 Associated PID—acute or chronic, pelvic kidney.
 Associated myoma, prolapse (procidentia), ovarian tumor or genital
fistula.
 Young patient (to preserve ovarian function).
 Vaginal stenosis — placement of radiation source is inadequate.
 Cases with adenocarcinoma or adenosquamous carcinoma — surgery is
preferred.

30. Radiation reactions
EARLY
1. anorexia, nausea, vomiting, lassitude or even fever
2. diarrhea (radiation enteritis)
3. leukopenia and thrombocytopenia, anemia
4. intestinal reaction such as enteritis, colitis, proctitis
5. urinary—cystitis, pyelitis, hematuria
6. Skin reaction such as peeling often found in moist area of the vulva. this is
almost absent in megavoltage radiotherapy

31. Radiation reactions
late (due to vasculitis and fibrosis):
 atrophic changes of vulval skin and vaginal stricture
 Radiation fibrosis
 pathological fracture due to osteoporosis
 stricture, bleeding per rectum, perforation, obstruction
 malabsorption syndrome with megaloblastic anemia
 Proctosigmoiditis
 radiation menopause

32. Radio sensitivity
 means the response of the tumor to irradiation. Radiosensitivity is measured in terms of loss of cellular
proliferative capacity due to the damage to DNA. Accumulation of sublethal injury following repeat
radiation leads to ultimate DNA damage and cell death.
 Radiosensitivity depends on several factors:
 Tissue hypoxia—higher the hypoxic fraction of cells, the less (2-3 times) is the radiation response.
Hypoxic cells are more resistant to radiation compared to toxic cells.
 Proportion of mitotic (clonogenic) cells— clonogenic cells are more radiosensitive.
 Cell cycle—mitotic cells (M phase) and G2 cells are more radiosensitive compared to late S-phase cells
 Tumor specificity—certain tumors (dysgerminomas) are more radiosensitive than the others.
 Tumor volume—smaller the tumor volume → lesser the hypoxic cells → less the radiation dose better the
radiation response.

33. Radio sensitivity
 Lesser the photon wavelength more is the penetrating power and energy
of ionizing radiation. Supervoltage and megavoltage radiation (60Co,
137Cs, 226Ra, betatron, linear accelerator) have the following advantages
over the orthovoltage one.
 They have higher energy of radiation, less skin injury, less lateral
scattering and more tissue penetration at a greater depth. They are
suitable for the deep seated tumors (e.g. carcinomas of the cervix and
endometrium).

34. Fractionation
 Is the division of a total dose of external beam radiotherapy into small (daily) doses.
Thus it spares normal tissue damage preferentially.
 External beam radiotherapy is usually fractionated and is given once daily for five
times a week. A dose of 180-220 cGy per fraction is used. This is based on the
ability of the cells to accumulate and repair the sublethal injury.
 Tumor tissue takes longer time to recover from radiation damage compared to
normal tissue. Fractionation allows normal tissue (intestinal mucosa, bone marrow)
to repair sublethal injury (sparing effect). On the other hand irradiation results in
accumulation of sublethal damage and ultimate loss of reproductive capacity in
tumor tissue.

35. Radiopotentiators and hypoxic cell sensitizers
Chemotherapeutic agents
 Cisplatin, paclitaxel ,Gemcitabine, doxorubicin
Others
 Metronidazole, misonidazole ,tumor necrosis factor (tnf), interferon, acyclovir
 Intraoperative radiation of large fraction of 1500-2500 cGy are delivered directly to the area
selected. Periaortic node irradiation (biopsy proven) at the time of staging laparotomy is
possible.
 Hyperthermia is found helpful as an active anti-neoplastic agent and a significant
radiosensitizer.

36. New technology for radiation therapy
 Three-dimensional conformal radiation therapy (3D CRT) uses imaging modalities (CT, MRI and PET
scaning). Beam placement using a CT simulation is used. 3D conformal therapy can shape the beam
to conform to the target. This can help to arrange the beams to maximize dose to the tumor and
minimize dose to normal tissues.
 Intensity modulated radiation therapy (IMRT): IMRT uses the power of computers to shape and
perform thousands of iterations of planning to maximize the tumor dose and to minimize normal
tissue dose. Both 3D CRT and IMRT use small collimator “leaves” to shape the beam finely. These
“leaves” are mobile and can vary the beam intensity. It allows irregular shapes (tumor) to be treated
and has the benefit of reduced radiation to normal tissues (bowel, bladder). Tomotherapy and cone-
beam CT may allow more precise localization of beam and verification of dose delivered.

37. New technology for radiation therapy
 Stereotactic radiotherapy and Gamma-Knife radiation are similar to IMRT
and 3D CRT to allow precise high dose delivery of external radiation.
Steoreatactic radiation uses a modification of linear accelerator

38.  Thank you