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Oncology-Total Body Irradiation (TBI)
I. What is TBI?
Total body irradiation (TBI) is a high-dose radiation therapy used to eliminate residual malignant disease and ablate bone marrow before stem cell transplantation. This is often combined with high-dose chemotherapy. The goal is to improve cure rates for sensitive tumors.
II. Aims of TBI:
  • Eliminate residual cancer: Destroy any remaining cancer cells.
  • Ablate bone marrow: Completely destroy the patient's existing bone marrow to allow successful engraftment (establishment) of donor stem cells.
  • Immune suppression: Reduce the immune system's response, especially crucial for non-haplotype identical grafts (where the donor's and recipient's HLA genes aren't completely matched).
III. Indications for High-Dose Therapy (using TBI):
  • Hematological malignancies: Relapsed acute leukemia, high-grade non-Hodgkin lymphoma (NHL), and myeloma often precede bone marrow or stem cell transplants that use TBI.
  • Other malignancies: Neuroblastoma is an example.
IV. Types of Hematopoietic Reconstitution (Bone Marrow Replacement):
  • Autologous: The patient receives their own stem cells (peripheral or cryopreserved marrow) harvested before high-dose therapy.
  • Allogeneic: The patient receives stem cells from a matched or mismatched donor (often a family member or from a donor registry). Mismatched grafts may be one haplotype identical.
V. Pre-Treatment Screening:
Crucial before TBI to assess patient suitability and mitigate risks:
  • Disease remission: The cancer must be in remission (dormant) before proceeding.
  • Organ function: Adequate renal (kidney), cardiac (heart), hepatic (liver), and pulmonary (lung) function is essential to handle treatment toxicity.
  • Medication assessment: Review medication history for potential interactions or side effects that could exacerbate TBI's effects, including:
    • Neurotoxicity: Asparaginase
    • Renal toxicity: Platinum, Ifosfamide
    • Pulmonary toxicity: Methotrexate (MTX), Bleomycin
    • Cardiac toxicity: Cyclophosphamide, Anthracyclines
  • Sanctuary sites: Assess the need for additional treatment to areas where cancer cells may hide (sanctuary sites), such as the central nervous system (CNS), testes, and mediastinum.
VI. Preparation for TBI:
  • Antiemetics: Administer intravenously (IV) to prevent nausea and vomiting. Commonly includes a 5-HT antagonist and dexamethasone.
  • Sedation: May require additional sedation with phenobarbital or diazepam. Ketamine anesthesia may be necessary for very young children.
VII. TBI Technique:
  • Linear accelerator: A linear accelerator is used, optimally with 6MV energy.
  • Fractionated TBI: Preferred for convenience, delivering radiation in smaller doses over several days.
  • Patient positioning: Patient lies on a couch behind a Perspex sheet (for consistent skin dose), alternating between side and back positions. Opposed fields are used for half the treatment time.
  • Distance: The couch is positioned at an extended distance to achieve the necessary body coverage.
  • Dose inhomogeneity: Dose distribution isn't uniform due to body shape and tissue density differences (e.g., lungs). Bolus or lung shielding may compensate, but often isn't necessary with the described schedules.
  • Dose-limiting organ: The lungs are the most vulnerable organ to radiation damage.
VIII. Dose Calculation:
  • Dosimetry: Paired lithium fluoride dose meters or diodes measure the dose distribution throughout the body. Readings are taken from defined sites (lung, mediastinum, abdomen, pelvis).
  • Midline dose: Averaging anterior-posterior (AP) and posterior-anterior (PA) readings.
  • CT scanning: Whole-body CT scans with planning software can also determine doses.
IX. Dose Schedules:
  • Adults: Optimal fractionated doses are 13.2-14.4 Gy (depending on the prescription point). The maximum lung dose (dose-limiting) shouldn't exceed 14.4 Gy.
  • Children: May tolerate slightly higher doses than adults. The MRC protocol uses eight 1.8 Gy fractions over four days. Many other schedules exist.
X. Toxicity of TBI:
A. Acute Effects (occurring shortly after treatment):
  • Nausea and vomiting: Start about 6 hours after the first fraction.
  • Parotid swelling: Occurs in the first 24 hours, resolving spontaneously.
  • Hypotension: Low blood pressure.
  • Fever: Usually controlled with steroids.
  • Diarrhoea: Occurs around day 5 due to gastrointestinal (GI) mucositis (inflammation of the mucous membranes).
B. Delayed Toxicity (occurring weeks to years later):
  • Pneumonitis: Lung inflammation causing shortness of breath and characteristic X-ray changes.
  • Somnolence: Sleepiness, anorexia (loss of appetite), and sometimes nausea (6-8 weeks post-treatment), resolves within 7-10 days.
  • Cataracts: Develop in <20% of patients, increasing in incidence for 2-6 years.< />pan>
  • Hormonal changes: Azoospermia (sterility in males) and amenorrhea (absence of menstruation) are common; occasional cases of maintained fertility exist.
  • Hypothyroidism: Thyroid damage, sometimes combined with pituitary damage.
  • Growth impairment (children): Impaired growth hormone production and early epiphyseal fusion (bone growth plate closure) lead to stunted growth.
  • Second malignancies: A 5-fold increased risk of developing new cancers, including brain tumors, oral and rectal carcinomas, and lymphoid system malignancies (due to prolonged immune suppression).
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