What are the acute and chronic adverse effects of radiation therapy for cancer?

Adverse Effects of Cancer Radiation Therapy

Radiation therapy causes both acute effects during treatment (dermatitis, fatigue, mucositis) and potentially serious late effects years afterward (cardiovascular disease, secondary cancers, organ dysfunction), with severity depending on radiation dose, treatment volume, fractionation schedule, and patient age at treatment. 1

Acute/Early Effects (During and Shortly After Treatment)

Skin Reactions (Radiation Dermatitis)

• Occurs in the majority of patients receiving radiotherapy, with 20-25% experiencing severe reactions 1
• Manifests within a few weeks of starting treatment, progressing from transient erythema to persistent erythema, dry desquamation, or moist desquamation 1
• Grade 3/4 skin toxicity rates: 7% with conventional fractionation, 11% with hyperfractionation and accelerated fractionation 1
• When combined with chemotherapy, rates increase dramatically: 54% grade 2,20% grade 3, and 4% grade 4 dermatitis 1
• Severity correlates with total radiation dose, dose per fraction, overall treatment time, beam energy, and exposed skin surface area 1

Systemic Acute Effects

• Fatigue, diarrhea, bladder irritation occur to some degree in most patients and are magnified by concurrent chemotherapy 1
• Site-specific effects include mucositis, xerostomia, weight loss, dysphagia, taste alteration, nausea, vomiting, and pain 1
• These acute effects typically resolve soon after radiation completion with supportive care 1

Late/Chronic Effects (Months to Years After Treatment)

Cardiovascular Toxicity

Cardiovascular disease is the third-leading cause of death in radiation-treated cancer survivors, particularly after mediastinal radiation 1

Coronary Artery Disease

• 2-7 fold increased relative risk of myocardial infarction after chest irradiation 1
• Cumulative 30-year coronary event incidence reaches 10% in Hodgkin lymphoma survivors 1
• Radiation-related cardiac disease typically manifests 15-20 years after treatment, with younger patients more susceptible 1
• Risk is proportional to radiation dose delivered to the heart 1

Valvular Disease

• Clinical valvular disease develops in up to 29% of children receiving radiotherapy, with substantially more aortic regurgitation, tricuspid regurgitation, and aortic stenosis 1
• Radiation-induced valvular heart disease includes fibrosis and calcification of the aortic root 1

Myocardial and Pericardial Disease

• Up to 37% of patients have abnormal left ventricular mass or end-diastolic dimension a decade and a half after radiation (average dose 40 Gy) 1
• Myocardial fibrosis leads to restrictive cardiomyopathy 1
• Chronic constrictive pericarditis may develop several years after completion of radiotherapy 1

Endocrine Dysfunction

• Cranial, orbital, infratemporal, and nasopharyngeal irradiation causes radiation-induced hypothalamic-pituitary injury, leading to growth hormone deficiency and central hypogonadism 1
• Pelvic, whole-abdomen, and lumbar/sacral spine radiation causes peripheral hypogonadism, especially when combined with alkylating chemotherapy 1
• Local radiation doses of 40 Gy associated with hyperthyroidism, which induces bone loss through osteoclast activation 1

Bone Health Complications

• Endocrine alterations from radiation affect bone growth, bone mass acquisition, and cause low bone mineral density 1
• Local and total body irradiation may directly affect bone mineral density by damaging bone marrow stroma 1
• Increased risk of subsequent bone neoplasms 1

Secondary Malignancies

• Most common sites of subsequent neoplasm include bone, skin, breast, thyroid, and central nervous system 1

Organ-Specific Late Effects

• Cardiovascular, cerebrovascular, gastrointestinal, hepatic, pulmonary, reproductive, and urinary system dysfunction can occur 1
• Neurocognitive, neurosensory, and neurological deficits may develop 1
• Risk of major complications (obstruction, fibrosis/necrosis, fistula) relates to radiation volume, total dose, dose per fraction, and tissue radiosensitivity 1

Risk Factors for Increased Toxicity

Treatment-Related Factors

• Higher total radiation dose and larger treatment volumes increase toxicity risk 1
• Shorter interfraction intervals (<4.5 hours between daily fractions) significantly increase late effects: grade 4 toxicity 8.6% vs 2.0% at 5 years 2
• Addition of chemotherapy to radiotherapy substantially increases acute side effects 1

Patient-Related Factors

• Younger age at treatment increases susceptibility to late cardiovascular effects 1
• Pre-existing conditions (inflammatory bowel disease, collagen-vascular disease, multiple abdominal/pelvic surgeries, pelvic inflammatory disease, diabetes) influence toxicity 1
• Sex and age at time of treatment affect late effects risk 1

Quality of Life Impact

• Association between radiation dermatitis occurrence and reduced patient quality of life has been documented 1
• Mean physical component score on SF-36 significantly lower in radiation-treated patients compared to age-matched national samples 1
• Severe acute reactions lead to enhanced late effects and adversely impact cosmesis 1

Prevention and Mitigation Strategies

• Complete entire radiation course (external beam and brachytherapy) within 8 weeks; delays decrease pelvic control by 0.5-1% per extra day 1
• Modern IMRT technology reduces toxicity by maximizing tumor dose while minimizing organ exposure 1
• Careful treatment planning with tight blocking minimizes normal tissue exposure without compromising tumor coverage 1
• Ovarian transposition before pelvic radiation in young patients (<45 years) prevents treatment-related menopause 1