Dose fractionation

Last updated

Dose fractionation effects are utilised in the treatment of cancer with radiation therapy. When the total dose of radiation is divided into several, smaller doses over a period of several days, there are fewer toxic effects on healthy cells. This maximizes the effect of radiation on cancer and minimizes the negative side effects. A typical fractionation scheme divides the dose into 30 units delivered every weekday over six weeks.

Contents

Background

Experiments in radiation biology have found that as the absorbed dose of radiation increases, the number of cells which survive decreases. They have also found that if the radiation is fractionated into smaller doses, with one or more rest periods in between, fewer cells die. This is because of self-repair mechanisms which repair the damage to DNA [1] [2] and other biomolecules such as proteins. These mechanisms can be over expressed in cancer cells, so caution should be used in using results for a cancer cell line to make predictions for healthy cells if the cancer cell line is known to be resistant to cytotoxic drugs such as cisplatin. [3] [4] The DNA self repair processes in some organisms is exceptionally good; for instance, the bacterium Deinococcus radiodurans can tolerate a 15 000 Gy (1.5 MRad) dose. [5]

This is a graph showing the effect of fractionation on the ability of gamma rays to cause cell death. The blue line is for cells which were not given a chance to recover; the red line is for cells which were allowed to stand for a time and recover. Effectofselfrepair.svg
This is a graph showing the effect of fractionation on the ability of gamma rays to cause cell death. The blue line is for cells which were not given a chance to recover; the red line is for cells which were allowed to stand for a time and recover.

In the graph to the right, called a cell survival curve, the dose vs. surviving fraction have been drawn for a hypothetical group of cells with and without a rest time for the cells to recover. Other than the recovery time partway through the irradiation, the cells would have been treated identically.

The human body contains many types of cells, and the human can be killed by the loss of a single type of cell in a vital organ. For many short-term radiation deaths due to what is commonly known as radiation sickness (3 to 30 days after exposure), it is the loss of bone marrow cells (which produce blood cells), and the loss of other cells in the wall of the intestines, that is fatal. [6]

Radiation fractionation as cancer treatment

Fractionation effects are utilised in the treatment of cancer with radiation therapy. When the total dose of radiation is divided into several, smaller doses over a period of several days, there are fewer toxic effects on healthy cells. This maximizes the effect of radiation on cancer and minimizes the negative side effects. A typical fractionation scheme divides the dose into 30 units delivered every weekday over six weeks. [7] [8]

Hypofractionation is a treatment regimen that delivers higher doses of radiation in fewer visits. The logic behind this treatment is that applying greater amounts of radiation works to lower the effects of accelerated tumor growth that typically occurs during the later stages of radiotherapy. [9]

Hyperfractionation is dividing the same total dose into more deliveries. Treatments are given more than once a day. Hyperfractionated radiation therapy is given over the same period of time (days or weeks) as standard radiation therapy. [10]

Accelerated fractionation (two deliveries per day and/or deliveries on weekends as well) has also been investigated. [11]

Related Research Articles

<span class="mw-page-title-main">Chemotherapy</span> Treatment of cancer using drugs that inhibit cell division or kill cells

Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

<span class="mw-page-title-main">Brachytherapy</span> Type of radiation therapy

Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. Brachy is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prostate, breast, esophageal and skin cancer and can also be used to treat tumours in many other body sites. Treatment results have demonstrated that the cancer-cure rates of brachytherapy are either comparable to surgery and external beam radiotherapy (EBRT) or are improved when used in combination with these techniques. Brachytherapy can be used alone or in combination with other therapies such as surgery, EBRT and chemotherapy.

The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes toxicity to the amount that causes the therapeutic effect. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

<span class="mw-page-title-main">Glioblastoma</span> Aggressive type of brain cancer

Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness.

<span class="mw-page-title-main">Proton therapy</span> Medical Procedure

In medicine, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often to treat cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that the dose of protons is deposited over a narrow range of depth; hence in minimal entry, exit, or scattered radiation dose to healthy nearby tissues.

<span class="mw-page-title-main">Radiosurgery</span> Surgical Specialty

Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy, it is usually used to treat cancer. Radiosurgery was originally defined by the Swedish neurosurgeon Lars Leksell as "a single high dose fraction of radiation, stereotactically directed to an intracranial region of interest".

<span class="mw-page-title-main">Carboplatin</span> Medication used to treat cancer

Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.

Palifermin is a truncated human recombinant keratinocyte growth factor (KGF) produced in Escherichia coli. KGF stimulates the growth of cells that line the surface of the mouth and intestinal tract.

<span class="mw-page-title-main">Fast neutron therapy</span>

Fast neutron therapy utilizes high energy neutrons typically between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors, cyclotrons (d+Be) and linear accelerators. Neutron therapy is currently available in Germany, Russia, South Africa and the United States. In the United States, one treatment center is operational, in Seattle, Washington. The Seattle center uses a cyclotron which produces a proton beam impinging upon a beryllium target.

<span class="mw-page-title-main">Satraplatin</span> Chemical compound

Satraplatin is a platinum-based antineoplastic agent that was under investigation as a treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.

Particle therapy is a form of external beam radiotherapy using beams of energetic neutrons, protons, or other heavier positive ions for cancer treatment. The most common type of particle therapy as of August 2021 is proton therapy.

Breast cancer management takes different approaches depending on physical and biological characteristics of the disease, as well as the age, over-all health and personal preferences of the patient. Treatment types can be classified into local therapy and systemic treatment. Local therapy is most efficacious in early stage breast cancer, while systemic therapy is generally justified in advanced and metastatic disease, or in diseases with specific phenotypes.

Stereotactic radiation therapy (SRT), also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy, is a type of external radiation therapy that uses special equipment to position the patient and precisely deliver radiation to a tumor. The total dose of radiation is divided into several smaller doses given over several days. Stereotactic radiation therapy is used to treat brain tumors and other brain disorders. It is also being studied in the treatment of other types of cancer, such as lung cancer. What differentiates Stereotactic from conventional radiotherapy is the precision with which it is delivered. There are multiple systems available, some of which use specially designed frames which physically attach to the patient's skull while newer more advanced techniques use thermoplastic masks and highly accurate imaging systems to locate the patient. The end result is the delivery of high doses of radiation with sub-millimetre accuracy.

<span class="mw-page-title-main">Radiosensitizer</span>

A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.

<span class="mw-page-title-main">PARP inhibitor</span> Pharmacological enzyme inhibitors of poly (ADP-ribose) polymerases

PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP).

<span class="mw-page-title-main">Cancer treatment</span> Overview of various treatment possibilities for cancer

Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy including small-molecule drugs or monoclonal antibodies, and PARP inhibitors such as olaparib. Other therapies include hyperthermia, immunotherapy, photodynamic therapy, and stem-cell therapy. Most commonly cancer treatment involves a series of separate therapies such as chemotherapy before surgery. Angiogenesis inhibitors are sometimes used to enhance the effects of immunotherapies.

<span class="mw-page-title-main">Temozolomide</span> Cancer medication

Temozolomide, sold under the brand name Temodar among others, is an anticancer medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. It is taken by mouth or via intravenous infusion.

<span class="mw-page-title-main">Abscopal effect</span> Hypothesis in the treatment of metastatic cancer

The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term “abscopal” in 1953 to refer to effects of ionizing radiation “at a distance from the irradiated volume but within the same organism.”

The host response to cancer therapy is defined as a physiological response of the non-malignant cells of the body to a specific cancer therapy. The response is therapy-specific, occurring independently of cancer type or stage.

References

  1. John Kimball (8 April 2012). "DNA repair". Archived from the original on 2018-02-12. Retrieved 2012-06-24.
  2. Ben Best. "Mechanisms of Aging" . Retrieved 2012-06-24.
  3. Niu, Nifang; Wang, Liewei (March 2015). "human cell line models to predict clinical response to anticancer drugs". Pharmacogenomics. 16 (3): 273–285. doi:10.2217/pgs.14.170. PMC   4358765 . PMID   25712190.
  4. Gillet, J.-P.; Calcagno, A. M.; Varma, S.; Marino, M.; Green, L. J.; Vora, M. I.; Patel, C.; Orina, J. N.; Eliseeva, T. A.; Singal, V.; Padmanabhan, R.; Davidson, B.; Ganapathi, R.; Sood, A. K.; Rueda, B. R.; Ambudkar, S. V.; Gottesman, M. M. (8 November 2011). "Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance". Proceedings of the National Academy of Sciences. 108 (46): 18708–18713. Bibcode:2011PNAS..10818708G. doi: 10.1073/pnas.1111840108 . PMC   3219108 . PMID   22068913.
  5. Bakermans, Corien (2015). Microbial Evolution under Extreme Conditions. Berlin: Walter de Gruyter. p. 154. ISBN   9783110340716.
  6. "Acute Radiation Syndrome: A Fact Sheet for Physicians". Centers for Disease Control and Prevention. 4 April 2018. Retrieved 7 November 2019.
  7. "Radiotherapy dose fractionation, second edition". The Royal College of Radiologists . 2016.
  8. Jones, Bleddyn; Morgan, David AL (2007). "Radiotherapy fractionation". In Dale, Roger G.; Jones, Bleddyn (eds.). Radiobiological modelling in radiation oncology. London: British Institute of Radiology. doi:10.1259/9780905749839.chapter04. ISBN   9780905749600.
  9. Pollack, Alan, and Mansoor Ahmed. Hypofractionation: Scientific Concepts and Clinical Experiences. 1st. Ellicot City: LimiText Publishing, 2011
  10. "Hyperfractionated radiation therapy". NCI Dictionary of Cancer Terms. National Cancer Institute. Retrieved 9 June 2018.
  11. "Accelerated-fraction radiation therapy". NCI Dictionary of Cancer Terms. National Cancer Institute. Retrieved 9 June 2018.