Summary of Normal-Tissue Dose Limits by Organ Tissue and Toxicity Endpoint for External-Beam Radiotherapy (EBRT) and Radiopharmaceutical Therapy (RPT)
| Tissue | Toxicity endpoint | Toxicity rate | EBRT limits* | RPT limits† | References |
|---|---|---|---|---|---|
| Brain | Symptomatic Necrosis | 5% | Dmax = 72 Gy | Unknown | (25) ‡ |
| Optic nerve/chiasm | Optic neuropathy | 5% | Dmax = 55–60 Gy | Unknown | (25) |
| Brain stem | Permanent cranial neuropathy or necrosis | 5% | Dmax = 54 Gy (small volume) | Unknown | (25) |
| 5% | Dmax = 59 Gy (1–10 cc) | ||||
| 5% | Dmax = 64 Gy (<1 cc) | ||||
| Spinal cord | Myelopathy | 5% | Dmax = 55–60 Gy | Unknown | (25) |
| Cochlea | Sensory-neural hearing loss (measured @ 4 kHz) | 30% | Dmean = 45 Gy | Unknown | (25) |
| Parotid-salivary glands | Long-term salivary function reduced to < 25% of pre–radiation therapy level | 20% | Dmean = 25 Gy (bilateral) | 9.2–33 Gy as single dose caused 25% incidence of transient xerostomia and 1 case of transient mucositis (4%) 131I-NaI has been reported to cause symptomatic xerostomia at doses as low as 5 Gy. | (25,72,76) |
| Larynx | Vocal dysfunction | 20% | Dmax = 66 Gy | Unknown | (25) |
| Aspiration | 30% | Dmean = 50 Gy | Unknown | (25) | |
| Edema | 20% | Dmean = 44 Gy | Unknown | (25) | |
| Pharynx | Symptomatic dysphagia and aspiration | 20% | Dmean = 50 Gy | Unknown | (25) |
| Thyroid | Clinical Hypothyroidism | 8% | Dmean = 45 Gy | Hypothyroidism common in 131I-MIBG and 131I-tositumomab therapies, but dose delivered unclear | (6) |
| Lungs | Symptomatic pneumonitis | 5% | Dmean = 7 Gy | Dmean > 30 Gy from single 90Y-microsphere¶ Tx (33% toxicity rate; n = 3); Dmean > 50 Gy cumulative from 90Y-microsphere Tx (50% toxicity rate; n = 2) Dmean > 27 Gy from 131I-radioimmunotherapy | (25,86,87) |
| < 20% | V20 < 30% (volume receiving > 20 Gy less than 30% of total lung volume) | ||||
| Heart | Pericarditis | 15% | Dmean = 26 Gy | Unknown | (25) |
| Long-term cardiac mortality | < 1% | V25 < 10% | Unknown | ||
| Esophagus | Grade > = 3 acute esophagitis | 5%–20% | Dmean = 34 Gy | Unknown | (25) |
| < 30% | Various dose volume constraints, ranging up to V70 < 20% | ||||
| Liver | Classical RILD | 5% | Dmean = 30–32 Gy | Data at the 5% toxicity rate level is inconclusive, but perhaps suggestive of Dmean = ∼35–50 Gy (glass 90Y-microspheres) and Dmean = ∼20–40 Gy (resin 90Y-microspheres). Package insert allows 80–150 Gy. Microsphere tolerance appears higher than agents targeting hepatocytes, but data limited. 90Y-ibirtumomab hepatic MTD > 28.5 Gy MIBG, approx. 30 Gy results in < 10% transient liver toxicity | (25,51–55,112) |
| 50% | Dmean = 42 Gy | Dmean > 70 Gy (glass 90Y-microspheres) Dmean = 52 Gy (resin 90Y-microspheres) | |||
| Stomach | Ulceration | 5%–7% | Uniform dose of ∼45 Gy | Unknown | (25) |
| Small bowel | Grade > = 3 acute toxicity | < 10% | V15 < 120 cc | Unknown | (25) |
| Spleen | Sepsis, Pneumonia | — | Data inconclusive, but suggestive of ∼20% chance of infection event after mean dose of 40 Gy to spleen | Unknown | (113) |
| Kidneys | End-stage renal disease | 5% | Dmean = 18 Gy (∼38 Gy BED) | 23–26 Gy (∼36 Gy BED) | (7,25) |
| 50% | Dmean = 28 Gy (∼44 Gy BED) | 34–38 Gy (∼44 Gy BED) | |||
| Bladder | Grade > =3 late toxicity (RTOG grading) | < 6% | Dmax < 65 Gy | Unknown | (25) |
| Penile bulb | Severe erectile dysfunction | 35% | Dmean = 50 Gy | Unknown | (25) |
| Rectum | Grade 2+ late rectal toxicity | < 15% | Various dose volume constraints ranging from V50 < 50% up to V75 < 15% | Unknown | (25) |
| Bone marrow | Moderate to severe hematopoietic syndrome | — | Acute WB exposure 2–5 Gy | Dmean > 2–3 Gy (131I-NaI, radioimmunotherapy, 90Y-DOTATOC, 131I-MIBG) | (36,85,88,114,115) |
| Hematopoietic syndrome w/anemia from GI syndrome | — | Acute WB exposure 6–7 Gy (LD50/60 with antibiotic and transfusion support) | — | (46) | |
| Pretransplant myeloablation | — | 12.0–13.5 Gy in ∼1.5 Gy WB exposures over 4–4.5 d | Dmean = ∼15 Gy (4.6–32.0 Gy; 131I-Iomab-B) | (89) | |
| Whole body | Moderate to severe hematopoietic syndrome | — | (See “Bone Marrow”) | MTD of 131I-Tositumomab determined to be 75 cGy the MTD for pretreated patients. MTD for patients who had HSC transplants = 65 cGy. MTD for patients with no prior therapy = 85 cGy | (92,93) |
*EBRT limits are for conventional fractionation unless otherwise stated.
↵†RPT limits are specified for β-emitting agents (i.e., 177Lu, 90Y, 131I).
‡Reference is provided for the QUANTEC summary article, for further details readers are referred to the tissue-specific QUANTEC documents.
↵¶Although 90Y-microspheres are typically treated as medical devices rather than radiopharmaceuticals under regulatory purview, they are included herein for completeness.