Oncology -Total Body Irradiation (TBI)

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.
• 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).