Radiation Therapy to Treat Cancer
The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy or brachytherapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.
Read the full article on the National Cancer Institute website.
Dangers of Radiation
Source: Accuray (manufacturer of radiation therapy equipment)
Important Safety Statement: Most side effects of radiotherapy, including radiotherapy delivered with Accuray systems, are mild and temporary, often involving fatigue, nausea, and skin irritation. Side effects can be severe, however, leading to pain, alterations in normal body functions (for example, urinary or salivary function), deterioration of quality of life, permanent injury and even death.
Radiation therapy to the chest can cause:
Source: Leukemia and Lymphoma Society
- Lung damage (scarring, inflammation, breathing difficulties)
- Heart damage (scarring, inflammation, coronary heart disease)
- Osteosarcoma (bone cancer)
- Breast cancer
- Thyroid cancer
- Hypothyroidism or hyperthyroidism
Radiation therapy may double the incidence of solid cancers
Radiation treatment generates therapy-resistant cancer stem cells from less aggressive breast cancer cells
Source: Wiley Online Library
Researchers from the Department of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center report that radiation treatment transforms cancer cells into treatment-resistant breast cancer stem cells, even as it kills half of all tumor cells.1
“When we look at early-stage cancer patients, we compare patients receiving exactly the same treatment, and some fail and some are cured, and we can’t predict who those patients will be,” says Frank Pajonk, MD, PhD, the study’s senior author and an associate professor of radiation oncology and Jonsson Cancer Center researcher.
In some cases, cancer stem cells are generated by the therapy, but scientists do not yet understand all the mechanisms that cause this to occur. If they can determine the pathway and remove the reprogramming of cancer cells, they ultimately may be able to reduce the amount of radiation given to patients along with its accompanying side effects, says Dr. Pajonk.
The investigators found that induced breast cancer stem cells (iBCSCs) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells in regenerative medicine.
In the study, Dr. Pajonk and colleagues eliminated the smaller pool of BCSCs and then irradiated the remaining breast cancer cells and put them in mice. They were able to observe the initial generation into iBCSCs in response to the radiation treatment through a unique imaging system. These new cells were highly similar to the BCSCs that had been found in tumors that had not been irradiated. They also found that these iBCSCs had a more than 30-fold increased ability to form tumors than the nonirradiated breast cancer cells.
Their findings show that if tumors are challenged by certain stressors that threaten them (such as radiation), they generate iBCSCs that may, along with surviving cancer stem cells, produce more tumors.
The researchers’ work continues as they begin to identify the pathways and several classes of drugs to prevent this process from occurring. To date, they have identified 2 different targets and drugs that could prevent it. The group has published their results of the study in breast cancer but also has made similar observations in both glioblastoma and head and neck cancer.
Dr. Pajonk says the study does not discredit radiation therapy. “Patients come to me scared by the idea that radiation generates these cells, but it truly is the safest and most effective therapy there is.”
1 Lagadec, C, Vlashi, E, Della Donna, L, Dekmezian, C, Pajonk, F. Radiation-induced reprogramming of breast cancer cells. Stem Cells. 2012;30:833–844.
Breast irradiation causes breast and lung cancer
Young women treated with radiotherapy for Hodgkin’s disease (HD) experienced a threefold increased risk of breast cancer, which rose with higher radiation doses to the breast. HD patients treated with radiotherapy had a sixfold risk of lung cancer, with risk related to dose of radiation received.
Women who received pelvic radiotherapy for cervical cancer were found to have a twofold risk of new cancers in organs that were heavily irradiated.
Source: Second Cancers – Landmark Studies
The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute
Radiotherapy treatments and their impact in reproductive health
Radiation therapy is a component of curative therapy for a number of diseases, including those presenting frequently in young patients such as breast cancer, Hodgkin’s disease, head and neck cancer and gynecologic cancers. It is often indicated for the treatment of prostate cancer as well.
It is known that cancer cells present with defects in their ability to repair sub-lethal DNA whereas normal cells have the ability to recover. Although radiation therapy is aimed to a loco-regional application and although cancer cells are the target, radiation may also induce damage to normal cells in the tissues.
The response to radiation therapy depends on various factors such as the phase of cell cycle the cells are (cells in late G1 and S are more resistant), the degree of cell ability to repair the DNA damage and other factors such as hypoxia (hypoxic cells are more resistant), tumor mass and growth fraction. Non-dividing cells are more resistant than dividing cells.
Except for the bone marrow, the most sensitive organs to radiation therapy in the body are the gonads, both the male testis and the female ovary. The extent of damage in the female and male gonads depends on the dose, fractionation schedule and irradiation field  . Radiation therapy can be administered as teletherapy, which aims at treating a large volume of tissue. For small volumes of tissue, such as in the case of cervix cancer in the female, radiation therapy can be administered in encapsulated sources of radiation that can be implanted directly into or adjacent to tumor tissue.
Whenever female reproductive organs are involved in the irradiated field, i.e., the ovaries, the uterus and the vagina may be compromised and damaged by direct irradiation. Scattered radiation may also damage reproductive organs. In the female, radiation therapy results in dose-related damage of the gonads by the destruction of primordial follicles, which constitute the nonrenewable follicle pool. In women, the degree and persistence of the damage is also influenced by age at the time of exposure to radiotherapy and due to a reduced reserve of primordial follicles in older women, the number of follicles remaining may be also be reduced at older ages . Table 2 presents a compilation of current knowledge on the impact of radiation doses and age at radiotherapy in male and female gonadal function . In general, a dose of about 2 Gy applied to the gonadal area destroys up to 50 % of the ovarian follicle reserve. In pediatric patients, failure in pubertal development may be the first sign of gonadal failure in both sexes. Total body irradiation (TBI) given in conjunction with myeloablative conditioning prior to bone marrow transplantation is one of the most toxic treatments for the gonads and it is highly related to gonadal failure in both sexes  .
In men, the gonadal stem cells responsible for the continual differentiation and production of mature spermatozoa, the spermatogoniae, are extremely sensitive to radiation. The Leydig cells, which are responsible for the hormonal production of testosterone, are on the contrary more resistant to radiotherapy and adult patients may thus preserve hormonal production although becoming infertile. In prepubertal boys, the sensitivity to radiation therapy of Leydig cells is greater than that of older males at very high doses . Prepubertal patients may retain Leydig cell function after radiation therapy during childhood and in those cases they will present with normal pubertal development and well-preserved sexual function later in life. Nevertheless, most of those patients present at adulthood with reduced testicular size, impaired spermatogenesis and infertility.
4.1. Gonadal shielding and ovarian transposition
The standard medical procedure currently offered to reduce scatter radiation to reproductive organs and preserve fertility in male and female patients, both adult and prepubertal, is the use of shielding. When shielding of the gonadal area is not possible, the surgical fixation of the ovaries in females far from the radiation field known as oophoropexy (ovarian transposition) may be considered. It is estimated that this procedure significantly reduces the risk of ovarian failure by about 50% and those patients may retain some menstrual function and fertility . Scattered radiation and damage of the blood vessels that supply the ovaries are related to the failure of this procedure .
4.2. Radiotherapy of the uterus
Radiotherapy of the uterus in young women and girls has shown to induce tissue fibrosis, restricted uterine capacity, restricted blood flow and impaired uterine growth during pregnancy, as shown by follow-up of cancer survivors  . The uterine damage seems to be more pronounced in the youngest patients at the time of radiotherapy. As a consequence, radiotherapy-treated female patients present with a high risk of unfavorable pregnancy outcomes such as spontaneous abortion, premature labor and low birth weight offspring  . Irradiation of the vagina is related to fertility and sexual issues due to loss of lubrication, anatomical impairments and in some cases vaginal stenosis.
4.3. Cranial irradiation and hormonal dysfunction
Cranial irradiation may induce disruption of the hypothalamic-pituitary-gonadal axis, which is a recognized potential complication that can lead to infertility in both female and male patients. Follow-up of female patients treated for brain tumors with cranial irradiation post- and pre-pubertally has evidenced a high incidence of primary hypothalamic and pituitary dysfunction with consecuent disturbance in gonadotropin secretion. In some cases, precocious puberty may also be induced by cranial irradiation in childhood, which has been attributed to cortical disruption and loss of inhibition by the hypothalamus.
Read the full article at Intech.com