Radiation Side Effects and Syndromes

Original Editors -Alicia Dupilka & Kristin Gramling from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Kristin Gramling, Alicia Dupilka, Lucinda hampton, Vidya Acharya, Kim Jackson, Admin, Elaine Lonnemann, WikiSysop, 127.0.0.1 and Wendy Walker

Definition/Description                                                   

Radiation therapy, or radiotherapy, is a common oncologic treatment modality utilising ionising radiation to control or eliminate malignant cells. Radiotherapy may be used alone, or synergistically with chemotherapy or immunotherapy. The type of radiation therapy employed depends on the disease and the specific type of cancer being treated.

Radiotherapy plays a part in:

1. Primary curative treatment (eg. head and neck cancer),
2. Adjuvant therapy (e.g. reducing recurrence rate after local breast cancer surgery)
3. Palliation of cancer symptoms (e.g. reducing pain from bone metastases).
4. Treating non-malignant disease, e.g. Graves thyroiditis, keloid scarring.

• Nearly two-thirds of all cancer patients will receive radiation therapy
• There are no good estimates of how many of these patients will develop complications due to the radiation therapy

Techniques

Radiotherapy is customarily divided into three main categories:

1. External beam radiotherapy (EBRT) where a medical linear accelerator (linac) directs ionising radiation at the tumour from outside the body eg

• • Conventional Radiation Therapy. This refers to the old techniques of radiation therapy where treatments would be planned by defining a limited number of beams with the boundaries delineated on orthogonal x-rays of the patient. It has been largely replaced by other highly conformal external beam radiation therapies, which use CT images to plan the treatment. Examples of these newer techniques include: three-dimensional conformal radiation therapy (3D-CRT); intensity-modulated radiation therapy (IMRT); stereotactic radiosurgery; electron therapy; particle (hadronic) therapy.

2. Sealed source radiotherapy (brachytherapy) where a radiation source(s) is placed, under the guidance of imaging, within or next to the area requiring treatment.

3. Unsealed source radiotherapy (systemic radioisotope therapy) where a radioisotope is delivered through: infusion e.g. for neuroendocrine tumours ; ingestion e.g for thyroid cancer.

Characteristics/Clinical Presentation

Side Effects

Depend on the area of the body being treated, dose given per day, total dosage, general medical condition and other treatments being given.

1. Acute radiation injury

• Nausea, malaise, dysphagia, vomiting immediately following irradiation
• Erythema
• Mucosal inflammation (stomatitis, esophagitis, enteritis, etc.)
• Bone marrow damage: anemia, thrombocytopenia, and/or leukocytopenia (pancytopenia)
• Infection due to immunocompromise
• Early radiation-induced lung injury (radiation pneumonitis): Dyspnea, dry cough, hemoptysis, and fever may occur several weeks following radiation.
• Partial respiratory insufficiency is an early sign.

2. Chronic radiation damage

• Radiation Fibrosis Syndrome
• Late radiation-induced lung injury (radiation fibrosis)
• Bone: fractures
• Bone marrow damage: anemia, thrombocytopenia, and/or leukocytopenia (pancytopenia); Infection due to immunocompromise
• Heart: increased risk of myocardial infarction
• Gastrointestinal: impaired function
• Thyroid: impaired function (hypothyroidism)
• Impaired fertility: Fibrosis in ovaries involving amenorrhea; Azoospermia
• Radiation of the head: Leukoencephalopathy; Hormone imbalances and their outcomes, such as stunted growth due to low growth hormone levels
• Xerostomia
• Malignancies: especially leukemias, MDS, lymphoma, thyroid cancer

Common general side effects of radiation therapy

Fatigue

Erythema

Hair loss

Low blood count

Other effects may include (not exhaustive list)

Radiation Fibrosis Syndrome

Progressive fibrotic tissue sclerosis resulting from radiation treatment

• It affects many different types of tissue including skin, muscle, ligaments, tendons, nerves, heart, lung, gastrointestinal and genitourinary tract, and bone; in order for a structure to be considered affected by this syndrome, it must be within the radiation field or have tendons, neurovascular innervation or lymphatic flow that travels in the field.
• The pathophysiology behind the sclerosis, fibrosis and atrophy is not well understood.  Some believe there is a link between vascular endothelial damage and the progression of the fibrosis.  When endothelial cells are damaged by radiation they can no longer get rid of the surrounding thrombin causing a profibrogenic effect on smooth muscle cells, fibroblasts, myofibroblasts and other cells.
• Problems may not present for several months or years after treatment
• Usually has a slow, insidious onset and is not reversible

    Risk Factors: Hodgkin lymphoma; Age; Overall health; Degenerative spine disease; Exposure to chemotherapy treatment; Location of radiation; Head and neck cancer, because high doses are needed and there are many vital tissues in that radiation field; Neuropathic pain due to RFS is more likely to occur in those with pre-existing medical disorders involving the nervous system such as  diabetes, spinal degeneration and cervical radiculopathy

Structures Affected:

Nerve

• Peripheral Nervous System (PNS): Pain, sensory loss and weakness caused by external compressive fibrosis of soft tissue and ischemia from fibrosis.
• Central Nervous System (CNS): Autonomic Nervous System can be affect resulting in orthostatic hypotension, bowel and bladder changes, and sexual dysfunction
• Neuropathic pain involving both the PNS and CNS is common.  It is due to damage of neural structures within the field of radiation.
• Sensory loss is also common including loss of light touch, pain, temperature, vibration and position sensation
• Weakness due to damage of neural structures, including plexopathy and mononeuropathies.

Muscle

• Painful spasms are common due to myopathies, weakened and fatigability of muscles and ectopic activity of the motor nerve
• Localized muscle pain due to sensitization of local pain neurons

Tendon and Ligaments

• Progressive fibrosis and sclerosis causing decreased elasticity, shortening and contractures
• Effects do not always have to be direct.  Radiation to the upper leg can cause ankle contractures because the muscles, tendons and vascular structures of the ankle run of the length of the leg.

Bone

• Decreased bone density
• Osteoradionecrosis of the mandible and fractures of the pelvis, hip, long bones and ribs are common
• Radiation in children may cause long bones and the spine to mature abnormally if the growth plate is affected

Common Clinical Syndromes Associated with RFS:

• Neck Extensor Weakness- severe atrophy of the cervicothoracic paraspinal and shoulder girdle musculature resulting from damage to the motor nerve and/or the muscle itself
• Shoulder Pain and Dysfunction - damage to the cervical nerve roots, brachial plexus, rotator cuff (RTC) muscles, rhomboids, and peripheral nerves innervating these muscles all contributes to this dysfunction.  May result in RTC tendonitis and adhesive capsulitis
• Cervical Dystonia - usually involving the SCM, scalenes, and trapezius.  If severe it can affect swallowing, phonation and activities of daily living.
• Trismus - impaired mouth opening can result from the invasion of the tumor into the masseter and pterygois muscles, the innervation of these muscles, or the TMJ.  It can affect chewing, swallowing, oral hygiene and pulmonary function.

Systemic Involvement

Gastrointestinal

• Radiation Esophagitis: often involved in radiation treatment for lung cancer especially when a chemosensitizer is also used. Symptoms usually resolve in 1 to 3 weeks after radiation is finished. Symptoms: abnormal peristalsis, odynophagia (pain with swallowing) and dysphagia
• Radiation Enterocolitis: often results in fibrosis leading to strictures in the intestines, bowel obstruction, fistulas with abscess formation, ulceration with bleeding and malabsorption
• Acute or Chronic Radiation Enteritis.
  

Pulmonary

• see Pulmonary Complications of Cancer

Cardiovascular

• Radiation Heart Disease - may result in pericarditis, coronary heart disease, myocardial disease and aortic-valve disease

Musculoskeletal

Connective Tissue Involvement - late changes such as fibrosis, atrophy and contraction is common especially in collagen

• In bones and limbs it can cause weakness, limb-length discrepancies and scoliosis
• It can result in edema and decreased range of motion 
• It can cause pelvic adhesions that result in painful motion and sometimes plexopathy
• In the circulatory and lymphatic system it can cause loss of elasticity on contractility of vessels. Even though the actual lymph vessels may maintain their shape, fibrosis in the surrounding tissue can inhibit growth of the vessels into tissues that need to be healed.

Nervous System      

• Acute symptoms: occur during treatment and include debilitating fatigue; cranial radiation may result in short-term memory loss, changes in behavior and cognition, decreased appetite, dry skin, hearing loss, hair loss and decreased salivation
• Subacute symptoms: occur 1 to 4 months after treatment and are not as common.  Radiation to the cervical spine may result in subacute myelopathy (Lhermitte's sign).  Radiation to the brainstem may result in ataxia, nystagmus and dysarthria
• Chronic symptoms: occur months to years after therapy and can include damage to the cerebral vasculature leading to coronary artery disease, transient ischemic attacks, stroke or myocardial infarction.
• Radionecrosis - results from whole-brain radiotherapy.  Secondary tumors may develop and the hypothalamic system may be affected. Symptoms: headache, changes in cognition and personality, focal neurological deficits and seizures. 
• Myelopathy - results from radiation of the spinal cord.  May present as Brown-Sequard syndrome or motor neuron syndrome.
• Plexopathy - results from damage to the brachial and lumbar plexuses.  Symptoms may include paresthesias, motor deficits, lymphedema and pain.

Integumentary

Radiation Dermatitis - common since it is involved in most radiation therapy

Medical Management

• Clinical trials to learn how to use radiation therapy more safely and effectively are being conducted by doctors and scientists.
• Working on improving image-guided radiation.
• Research is also being done on radiosensitizers and radioprotectors.
• The use of carbon ion beams is still being investigated and remain experimental. This type of therapy are not currently available in the US.

Physical Therapy Management

Physical therapists should always wash their hands before treating a patient who has undergone radiation therapy to protect that client from possible infection.

Skin Care

• Avoid use of alcohol/drying agents, lotion, gel, or oil. Creams and gels can increase the dosage received on the skin and increase the likelihood of side effects
• Do not wash away markings of the targeted area
• Position the patient so they are not lying on the targeted area
• Avoid exposing the patient to sources of heat, including direct sunlight and modalities
• Monitor wound healing

Musculoskeletal 

• If adhesions are present in the hip after radiation of the pelvis, be sure to incorporate range of motion activities; early intervention is important to prevent contractures and restrictive scarring.
• Post-radiated tissue can tear when stretching so it is important to observe for blanching of the skin during stretching and not to stretch beyond that point.  Stretching should be continued 18 to 24 months after radiation therapy has been discontinued.

Nervous System 

• Anyone with neurological signs or symptoms of an unknown cause should be asked about a previous history or cancer and radiation therapy

Infection

• Therapists should observe carefully for signs of infection in patients who have undergone radiation treatment.  The first and only sign may be a fever because the patient may be immunosuppressed and their body cannot create a normal inflammatory response.

Exercise 

• A successful protocol should include patient education, exercise evaluation and an individualized exercise prescription. - Therapists must monitor vital signs in patients who have undergone radiation treatment because radiation and chemotherapy can leave the lungs and heart tissue permanently scarred. Patients should be taught to monitor their own vitals including heart rate, respiration rate and rate of perceived exertion (should not exceed 15 to 17) and taught to detect signs of complications such as dyspnea, pallor, excessive perspiration, or fatigue while exercising.  Patients should be told not to exercise within 2 hours of chemotherapy or radiation therapy because it increases the circulation and may increase the effects of the treatment.
• Studies have shown low to moderate intensity aerobic exercise during the same weeks of radiation treatment can help improve physical function and lower subjective levels of fatigue, anxiety, depression and sleep disturbances.

Management of Syndromes Associated with Radiation Fibrosis Syndrome

  Physical Therapy is usually the first line of treatment for the dysfunctions listed below.

• Neck Extensor Weakness - emphasize postural retraining through core strengthening, flexibility of the shoulder musculature, and strengthening the cervicothoracic and rotator cuff muscles.  This will help reduce energy demands and pain.  It is also important to develop a long-term home exercise program
• Shoulder Pain and Dystonia - treated through conservative measures because shoulder surgery should be avoided in patients with RFS because damage of the neruomuscular structures often results in poor surgical outcomes.  Work on core strength and posture, neck extensor and rotator cuff strength and stretching of pectoral girdle musculature in order to try to restore normal anatomical alignment of the shoulders. There is a potential long-term benefit if the patient consistently follows a home exercise program.
• Cervical Dystonia - the goal is to restore and maintain neck range of motion and a long-term home exercise program should be utilized.
• Trismus - Literature is limited but a variety of jaw-opening devices are available to help treat trismus.

Resources

Radiation Side Effects Worksheet http://www.cancer.org/acs/groups/content/@nho/documents/document/acsq-009503.pdf