Paul B. Romesser, Neil B. Desai, and Joachim Yahalom
TOTAL BODY IRRADIATION
TBI is a technique often incorporated into myeloablative & nonmyeloablative regimens in pts undergoing HSCT for a variety of malignant & nonmalignant disorders (Leibel & Phillips, Text book of Radiation Oncology 3rd ed.; Chapter 15).
• Goals of therapy include immunosuppression through lymphocyte & aberrant cell eradication. TBI also serves as kill residual leukemia & lymphoma cells
• Dose varies across institutions. Full-dose TBI is given in several fractions at doses to 1375 cGy in adults & 1500 cGy in children at MSKCC. Low-dose TBI (200–400 cGy) is given to pts undergoing reduced intensity conditioning regimens (often in cord blood programs & older pts).
• Chemotherapy is combined w/ TBI to achieve the above goals.
• Given the concern for radiation-related morbidity, interest in purely chemotherapeutic ablative regimens has increased.
Chemotherapy alone non-TBI regimens are in turn balanced by toxicities of ↑ cytoxic chemotherapy dose, reduced efficacy, & ↑ incidence of GVHD of unclear etiology.
Low-dose TBI regimens w/min. toxicity are ↑ in use for appropriate transplants.
Conditioning regimen selection is usually dictated by pt- & disease-specific factors.
• Opposed anterior–posterior (AP) & posterior–anterior (PA) fields w/pt standing upright aided by a specifically designed apparatus at an extended distance from the LINAC (Int J Radiat Oncol Biol Phys 1983;9:1607). On occasion, supine positioning on the floor can be used for severely deconditioned pts or young children.
• An acrylic spoiler is often used to ↑ the body surface dose.
• For full-dose TBI pts, lung blocks are used to partially shield the lungs from the fully penetrating photon beam in an effort to reduce the risk of acute pneumonitis & late pulm fibrosis. Matched, superficially treating electron beam fields are used to compensate dose to the CW in these areas. No blocking is required in low-dose TBI.
• Male pts receive a testicular electron boost to reduce risk of sanctuary site relapse.
Acute Toxicity With Full-dose TBI
• Common s/e w/in the first 24 h include nausea (90%), vomiting (80%)—effectively treated w/antiemetics, HA (40%), transient xerostomia (60%), mild parotitis (75%), & fever (40%) (Radiother Oncol2000;54:157).
• Dermatologic: Erythema & alopecia are commonly seen w/in the first wk.
• Parotitis: Apoptosis of serous cells → serum amylase peaking 1–2 d post RT. Effect is dose dependent w/spontaneous resolution of soreness in 5–6 d.
• Supportive care: Prophylactic ondansetron drip & IVF is standard & enables the majority of pts to tolerate combination cytoxic Rx & TBI conditioning regimen uneventfully.
Sub-acute Toxicity of Full-dose TBI
• Pneumonitis: Clinical dx w/pts typically presenting 1–2 mos post full-dose TBI w/a dry cough, new or worsening DOE, & a low-grade fever. Treatment consists of prednisone (1 mg/kg) for 2–3 wks w/a slow taper over 1–3 mos. A rapid taper can re-exacerbate the pneumonitis requiring reinitiation of treatment.
• VOD: Commonly seen 1–4 wks after HSCT as painful hepatomegaly, jaundice, & ascites.
Late Toxicity of Full-dose TBI
• Pneumonopathy: Etiology likely multifactorial.
• Pulm fibrosis: Presents as new or worsening DOE w/a ↓ diffusion capacity noted on PFTs.
• DAH: Potentially fatal complication.
• Idiopathic PNA syndrome
• CV toxicity: Given the ↓ dose to the heart & lungs, not commonly seen, but pts should be followed closely to asses for potential cardiovascular toxicity that could be seen y or decades after TBI.
• Cataracts: Common treatment-associated complication (15%) that presents as painless gradual vision loss w/lens opacification noted on PEx.
• Infertility: Infertility is seen in virtually all male pts & in females 10 y of age & older treated w/TBI. Pts are counseled to consider sperm/egg banking.
• Hypothyroidism: Most common endocrinopathy seen after TBI w/an incidence of approximately 25%. Pts require annual screening for hypothyroidism & early initiation of thyroid hormone replacement if identified.
• Endocrinopathies: ↑ risk of diabetes & lipid/cholesterol disorders.
• Impaired growth: Pertinent to prepubescent pediatric pts treated w/TBI. Etiology likely multifactorial.
• Impaired cognitive development: Subtle finding identified on neuropsychological testing corresponding to an approximate 3-point IQ loss in children.
• Secondary malignancies: ↑ rates of leukemias, MDS, PTLD, & an approximate two-fold risk for the development of solid tumors. TBI pts should be followed closely to monitor for potential secondary malignancies, w/an approximate two fold ↑ in the rates of many solid tumors.
TOTAL SKIN ELECTRON BEAM (TSEB)
• TSEB Rx is a technique to treat cutaneous T-cell lymphoma (CTCL), particularly mycosis fungoides (MF) (Perez & Brady’s Principles & Practice of Radiation Oncology 5th ed., Chapter 77).
• Mechanism of Rx includes homogeneous delivery of IR to highly radiosensitive CTCL cells.
• Goals of Rx include inducing remission in definitive treatment of newly diagnosed, nonlocalized CTCL & palliation.
• TSEB can be used as upfront Rx followed by adjuvant oral & cytoxic systemic agents and/or phototherapy or as second-line Rx.
• Early treatment does not preclude the use of repeat TSEB for palliation.
• Pts w/localized disease (Stanford I, AJCC IA) are more appropriate for localized radiotherapy fields, systemic and/or topical agents.
• The target of Rx includes skin varying from <0.5 mm (eyelid) to >5 mm (back), SC infiltration (>1.5 cm), blood present in the skin during irradiation, & superficial LN (up to 2–3 cm). The superficial nature of electron irradiation is preferred for treatment of CTCL.
• Modern techniques use a photon beam passed through a Lucite screen in front of the pt to generate the electron beam. This electron field is then used to treat the pt in multiple standing positions (MSKCC: 6-position, twice-weekly) for dose homogeneity. Disease response is typically brisk.
• Supplemental boost dose given to top & soles of feet, perineum, & occasionally under breast.
• Shielding of the eyes & digits of the hands/feet is used to reduce reaction due to Sn & field overlap.
• At >10 Gy, mild erythema w/dry desquamation w/brisk changes at lesions.
• At >25 Gy, transient edema of the hands & ankles w/blisters requiring local shielding or treatment breaks occur.
• Temporary nail loss & alopecia (100% by end of treatment) w/4–6 mo time to regen.
• Long-term sequelae are unusual at <10 Gy & uncommon at typical doses through 25 Gy. These are most commonly chronic cutaneous changes such as wrinkling, telangiectasias, uneven pigmentation, & reduced sweat gland function requiring care in hot environments. Rarely, permanent alopecia & SC fibrosis can occur. ↑ radiation-induced cutaneous neoplasia has been observed in pts receiving additional Rx along w/other agents.