Whole-body Irradiation
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Total body irradiation (TBI) is a form of
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s are often partially shielded to lower the risk of radiation-induced lung injury. Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune system, preventing immunologic rejection of transplanted donor
bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
or blood stem cells. Additionally, high doses of total body irradiation can eradicate residual cancer cells in the transplant recipient, increasing the likelihood that the transplant will be successful.


Dosage

Doses of total body irradiation used in bone marrow transplantation typically range from 10 to >12  Gy. For reference, an unfractionated (i.e. single exposure) dose of 4.5 Gy is fatal in 50% of exposed individuals without aggressive medical care. The 10-12 Gy is typically delivered across multiple fractions to minimise toxicities to the patient. In modern practice, total body irradiation is typically fractionated, with smaller doses delivered in several sessions, rather than delivering the entire dose at once. Early research in bone marrow transplantation by
E. Donnall Thomas Edward Donnall "Don" Thomas (March 15, 1920 – October 20, 2012)Frederick R. Appelbaum.Perspective: E. Donnall Thomas (1920–2012) Science 338(6111):1163, 30 November 2012 was an American physician, professor emeritus at the University o ...
and colleagues demonstrated that this process of splitting TBI into multiple smaller doses resulted in lower toxicity and better outcomes than delivering a single, large dose. The time interval between fractions allows other normal tissues some time to repair some of the damage caused. However, the dosing is still high enough that the ultimate result is the destruction of both the patient's bone marrow (allowing donor marrow to engraft) and any residual cancer cells. Non-myeloablative bone marrow transplantation uses lower doses of total body irradiation, typically about 2 Gy, which do not destroy the host bone marrow but do suppress the host immune system sufficiently to promote donor engraftment.


Usage in other cancers

In addition to its use in bone marrow transplantation, total body irradiation has been explored as a
treatment modality A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...
for high-risk Ewing sarcoma. However, subsequent findings suggest that TBI in this setting causes toxicity without improving disease control, and TBI is not currently used in the treatment of Ewing sarcoma outside of clinical trials.


Fertility

Total body irradiation results in infertility in most cases, with recovery of gonadal function occurring in 10−14% of females. The number of pregnancies observed after hematopoietic stem cell transplantation involving such a procedure is lower than 2%. Fertility preservation measures mainly include
cryopreservation of ovarian tissue Ovarian tissue cryopreservation is cryopreservation of tissue of the ovary of a female. Indications Cryopreservation of ovarian tissue is of interest to women who want fertility preservation beyond the natural limit, or whose reproductive potential ...
, embryos or oocytes. Gonadal function has been reported to recover in less than 20% of males after TBI.


References

{{authority control Transplantation medicine Radiobiology