Radiation Side Effects and Syndromes

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

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

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Definition/Description

Radiation therapy is when radiation is delivered to a specific area of the body to try and treat a disease, usually cancer.  The goal of the radiation is to kill rapidly dividing cancer cells while sparing slower dividing somatic cells. Radiation is usually used in conjuction with surgery or chemotherapy. 

The radiation may be delievered by a machine outside the body (external-beam radiation therapy) or it may come from radioactive material placed in the body (internal radiation therapy, also called brachytherapy).

Type of radiation used depends on:
• Type of cancer
• Size
• Location
• How close the cancer is to normal tissues
• How far the radiation needs to travel
• General health and medical history
• Other types of treatment
• Age and other medical conditions

External-beam radiation therapy: most often delivered in the form of photon beams (x-rays or gamma rays)

 3-Dimensional Conformal Radiation Therapy (3D-CRT): most common type

Intensity-Modulated Radiation Therapy (IMRT)

     • Dosage is chosen for different areas of the tumor and surrounding tissues
     • High-powered computer program calculates the required number of beams and angles
     • Goal: increase the dose to areas that need it and reduce exposure to sensitive areas
     • Can reduce the risk of some side effects
     • Larger volume of normal tissue overall is exposed

 Image-Guided Radiation Therapy (IGRT)

     • Repeated imaging scans performed during treatment
     • Can increase the accuracy and may allow reduction in planned volume of tissue to be treated
     • Decreasing total radiation dose to normal tissue

Tomotherapy

     • Type of image-guided IMRT
     • Hybrid between a CT and an external-beam radiation therapy machine
     • Sparing normal tissue from high radiation doses

Stereotactic Radiosurgery

     • Can deliver one or more high doses of radiation to a small tumor
     • Extremely accurate image-guided tumor targeting and positioning
     • High dose of radiation can be delivered without excess damage to normal tissue

Stereotactic Body Radiation Therapy

     • Radiation therapy in fewer sessions
     • Uses smaller radiation fields and higher
     • Treats tumors that lie outside the brain and spinal cord
     • Usually given more than one dose
     • Can treat only small, isolated tumors; including cancers in the lung and liver

 Proton Therapy

     • Deposit much of their energy at the end of their path (Bragg peak) and deposit less energy along the way
     • Should reduce the exposure of normal tissue

Internal-beam radiation therapy (Brachytherapy):

Interstitial: uses radiation source placed within tumor tissue

Intracavitary: uses a source placed within a surgical cavity or a body cavity

Episcleral: used to treat melanoma inside the eye, uses a source that is attached to the eye

Low-dose: recieve continuous low-dose radiation over a period of several days

High-dose: robotic machine attached to delivery tubes placed inside the body, can be given in one or more treatment session, cause less damage to normal tissue

Placement is either permanent or temporary

Permanent
•Surgically sealed within the body and left
• Remaining material does not cause any discomfort or harm
• Low-dose rate

Temporary

    • Carrier and the radiation sources are removed after treatment
    • Can be either low-dose or high-dose

Systemic Radiation Therapy

Swallows or receives an injection of a radioactive substance or a radioactive substance bound to a monoclonal antibody

Examples: radioactive iodine, ibritumomab tiuxetan (Zevalin®), combined tositumomab and iodine I 131 tositumomab (Bexxar®), samarium-153-lexidronam (Quadramet®), and strontium-89 chloride (Metastron®)

Prevalence

Nearly two-thirds of all cancer patients will recieve radiation therapy.

Characteristics/Clinical Presentation

Early (acute) and late (chronic)
Depend on the area of the body being treated, dose given per day, total dosage, general medical condition, other treatments being given

Side Effects

Acute
     • Skin irritation
     • Damage at regions exposed (salivary glands or hair loss if head or neck treated)
     • Urinary problems (lower abdomen treated)
     • Fatigue
     • Nausea with or without vomiting
     • Most disappear after treatment ends (some may be permanent)

Chronic
     • May or may not occur
     • Fibrosis (replacement of normal tissue with scar tissue)
     • Damage to the bowels
     • Memory loss
     • Infertility
     • Second cancer (rare); highest in those treated for cancer as a child or adolescent
     • Some chemotherapy drugs, genetic risk factors, and lifestyle factors can also increase risk of late side effects

Lymphedema

• Swelling that occurs when protein-rich lymph fluid accumulates in the interstitial tissue
• May contain plasma proteins, extravascular blood cells, excess water, and parenchymal products
• Often insidious
• Characteristics
     o Non-pitting swelling of either the arm or leg and usually involves the digits
     o Early stages: manifest pitting edema until fibrosis develops
     o May predispose to recurrent skin infections
• Complaints
     o Heaviness or fullness of the limb
     o Tight sensation of the skin
     o Decreased flexibility
     o Ambulation may be affected
• Risk factors
     o Undergoing axillary surgery/radiation therapy
     o Extent of local surgery
     o Local radiation
     o Delayed wound healing
     o Tumor causing lymphatic obstruction
     o Scarring of the left or right subclavian lymphatic ducts
• Grades
     o Grade 1: 5-10% interlimb discrepancy in volume or circumference, pitting edema
     o Grade 2: >10-30% interlimb discrepancy in volume or circumference, obliteration of skin folds, readily apparent deviation from normal contour
     o Grade 3: >30% interlimb discrepancy in volume; lymphorrhea; gross deviation from normal contour interfering with activities of daily living
     o Grade 4: progression to malignancy, amputation indicated, disabling

Associated Co-morbidities

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Medications

Amifostine is the only drug approved by the FDA to protect normal tissues (radioprotector)

Diagnostic Tests/Lab Tests/Lab Values

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Etiology/Cause

Risk Factors:

Dependent on organ radiated, individual tolerance, tumor type, volume radiated and fraction size/dosage.

Neurotoxicity

- High total dose and fractionation dose

- Large volume radiated

- Increased edema

- Age <12 or >60 years

- Concurrent chemotherapy

- Underlying diseases affecting the vascular structures (Diabetes, HTN)

- Stereotactic radiation surgery and brachytherapy (internal radiation)

Dermatitis

- Total dose/volume and fractionation dose

- Surface area exposed

Acute Enterocolitis

- Large volume

- High total dose and fractionation dose

- Concurrent chemotherapy

Chronic Entercolitis

- Older age

- Postoperative radiation

- Presence of collagen vascular disease

- Concurrent chemotherapy

- Poor radiation technique

Pulmonary

- Older age

- Lower performance status

- Lower pulmonary baseline function

- Large volume treated

Systemic Involvement

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Medical Management (current best evidence)

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 (current best evidence)

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Alternative/Holistic Management (current best evidence)

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Differential Diagnosis

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Case Reports/ Case Studies

Nozu T, Yoshida Y, Ohira M, Okumura T. Severe hyponatremia in association with I(131) therapy in a patient with metastatic thyroid cancer. Intern Med. 2011;50(19):2169-74. DOI: 10.2169/internalmedicine.50.5740

Abstract

Hyponatremia is a common clinical problem that results from various causes. Hypothyroidism is known to be one of the causes of this disorder. We report a case of metastatic thyroid cancer presenting with severe hyponatremia in association with hypothyroidism induced by pretreatment of I(131) therapy, such as a low-iodine diet and withdrawal of thyroid hormone. Serum arginine vasopressin (AVP) was elevated and urine osmolality was higher than that of serum. Saline infusion and thyroid hormone replacement normalized serum sodium and AVP. Inappropriate secretion of AVP in hypothyroid state was thought to be one of the causes of this hyponatremia.

Sonawane S, Gadgil N, Margam S. Therapy related myelodysplastic syndrome: a case report and review of literature. Indian J Pathol Microbiol. 2011 Apr-Jun;54(2):371-3. doi: 10.4103/0377-4929.81643.

Abstract

Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS) 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

fibrosis after proton beam therapy for non-small cell lung cancer. Jpn J Clin Oncol.2012 Oct;42(10):965-9. Accessed April 10, 2013.

Abstract

There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis.

Resources

Radiation Therapy and You: Support for People with Cancer

http://.www.cancer.gov/cancertopics/radiation-therapy-and-you)

Recent Related Research (from Pubmed)

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