Gastrointestinal radiation injury: Symptoms, risk factors and mechanisms

Table 1 Example of some gastrointestinal symptoms grades following radiation injury

Grade	Gastrointestinal symptoms
	Nausea
1	Loss of appetite without alteration in eating habits
2	Oral intake decreased without significant weight loss, dehydration or malnutrition; IV fluids indicated < 24 h
3	Inadequate oral caloric or fluid intake; IV fluids, tube feedings, or TPN indicated ≥ 24 h
4	Life-threatening consequences
5	Death
	Anorexia
1	Loss of appetite without alteration in eating habits
2	Oral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated
3	Associated with significant weight loss or malnutrition (e.g., inadequate oral caloric and/or fluid intake); IV fluids, tube feedings or TPN indicated
4	Life-threatening consequences
5	Death
	Haemorrhage-GI
1	Mild, intervention (other than iron supplements) not indicated
2	Symptomatic and medical intervention or minor cauterization indicated
3	Transfusion, interventional radiology, endoscopic, or operative intervention indicated; radiation therapy (i.e., hemostasis of bleeding site)
4	Life-threatening consequences; major urgent intervention indicated
5	Death
	Ulceration-GI
1	Asymptomatic, radiographic or endoscopic findings only
2	Symptomatic; altered GI function (e.g., altered dietary habits, oral supplements); IV fluids indicated < 24 h
3	Symptomatic and severely altered GI function (e.g., inadequate oral caloric or fluid intake); IV fluids, tube feedings, or TPN indicated ≥ 24 h
4	Life-threatening consequences
5	Death
	Incontinence anal
1	Occasional use of pads required
2	Daily use of pads required
3	Interfering with ADL; operative intervention indicated
4	Permanent bowel diversion indicated
5	Death

According to the Common Terminology Criteria for Adverse Events system v 3.0. IV: Intravenous; GI: Gastrointestinal; ADL: Activities of daily living; TPN: Total parenteral nutrition.

Table 2 Summary of risk factors for gastrointestinal radiation injury

Risk factors
Radiation techniques	Treatment volume, total dose, fractionation dose and schedules
Combined modality therapies	Surgery
	Chemotherapy: Particularly concurrent
Medical co-morbidities	Vascular disease, connective tissue disease, inflammatory bowel disease, HIV
Genetic susceptibility	Single nucleotide polymorphism, ataxia telangiectasia

HIV: Human immunodeficiency virus.

Table 3 Acute and chronic manifestations of gastrointestinal radiation injury

Clinical manifestations	Radiation tolerance doseTD5/5, TD50/5 (Gy)	Gastrointestinal organ
Oral mucositis occurs in > 90% of patients with concurrent chemotherapy[40]	Parotid gland: TD5/5 (32) TD50/5 (46)[60,179,180]	Mouth, salivary glands, hypopharynx, parotid
Xerostomia and altered saliva composition
Acute Grade 3-4 oesophageal injuries occur in 46%with concurrent chemotherapy[181]	TD5/5 (55-60)
Dose > 58 Gy predicts Grade 3-5 acute oesophagitis[54]	TD50/5 (68-72)[60,179]	Oesophagus
60 Gy resulted in Grade 3 toxicity in 42%[182]
Radiation can lead to late stricture and/or perforation of the oesophagus[53,60]
40 Gy: Severe late toxicity in 7% including ulceration, gastritis and small-bowel obstruction/perforation[183]	TD5/5; (50-60) TD50/5 (65-70)[60,179]	Stomach
Elevated liver enzymes in 5%[184]	TD5/5; (30-50)	Liver Small intestine
(31.3-37 Gy resulted in RILD in 9.4%[66,185]	TD50/5; (40-55)[60,179]
45 Gy cause 5% Grade 3-4 toxicity and 14% with concurrent chemotherapy[71]	TD5/5; (40-50)
Diarrhoea, abdominal pain in 20-70%[72]	TD50/5; (55-60)[60,179,180]
Transmural fibrosis leading to obstruction in 5%-10%[68,77-78]
Intestinal fistulation occurs at a rate of 0.6% to 4.8%[68,79]		Colon and rectum
50 Gy 5 year estimate of small bowel obstruction is 11%[186]
Colitis in 25%-50% of patients[186]	Colon
Grade 2-3 acute proctitis 40%[91]	TD5/5; (45-55)
Chronic rectal symptoms in 6.7%-31%[91]	TD50/5 (55-65)[60,179,180]
Acute symptoms of anus and rectal injury occur in up to 75% of patients during radiotherapy[187]	Rectum
	TD5/5; (60-61.38)
	TD50/5 (80-81.38)[60,179,180]

TD5/5: Radiation dose associated with 5% of patients’ risk of delayed toxicity in 5 years; TD50/5: The radiation dose associated with 50% of patients’ risk of delayed toxicity in 5 years. RILD: Radiation-induced liver disease.