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Radiotherapy causes DNA break and subsequent cell death. This affects the cancer cells more severely than the normal cells. However, with the growing number of patients receiving chemotherapy, providers come across patients who develop side effects of radiotherapy. Early recognition and prompt management of the acute side effects can prevent the persistence of these effects in the long term. This activity reviews the evaluation and treatment of radiation toxicity in different cancers and highlights the role of the interprofessional team in evaluating and treating patients with this condition. Objectives: Review the pathophysiology and common side effects of radiation therapy. Outline strategies for the treatment of radiotherapy side effects. Describe the importance of careful patient selection and tailored radiotherapy regimens to minimize complications. Explain the importance of monitoring the development of late side effects in long-term radiotherapy survivors. Access free multiple choice questions on this topic.

Overall, cancer rates are projected to increase from approximately 9 million in 2017 to approximately 26 million new cancer cases by 2030.[1][2] About 30% to 50% of all cancer patients receive irradiation either alone or with chemotherapy and surgery.[3] Therefore, around 7 million patients receive radiotherapy worldwide every year. Improved cure rates of all malignancies have resulted in more providers being confronted with a large number of patients with a wide range of chronic morbidities in long-term survivors. Hence all providers must be aware of the common adverse effects of radiation therapy. There are different types of radiation therapy. Two major types are external-beam radiation therapy and internal radiation therapy. External-beam radiation therapy is the most common type and delivers radiation from a machine outside the body. The types of external-beam radiation therapy are: Three-Dimensional Conformal Radiation Therapy (3D-CRT) - Three-dimensional pictures of the cancer are created, from CT or MRI scans. This allows aiming the radiation therapy more precisely. It means that higher doses of radiation therapy can be used while reducing damage to healthy tissue. This lowers the risk of side effects. Intensity Modulated Radiation Therapy (IMRT) - This is a more complex form of radiation. With IMRT, the intensity of the radiation is varied within each field unlike conventional 3D-CRT, which uses the same intensity throughout each beam. IMRT targets the tumor and avoids healthy tissue better than conventional 3D-CRT. Proton Beam Therapy - This treatment uses protons rather than x-rays. At high energy, protons can destroy cancer cells. The protons deposit the specific dose of radiation therapy to the targeted tissue. There is very little radiation dose beyond the tumor as compared to x-rays. This limits damage to nearby healthy tissue. Image-Guided Radiation Therapy (IGRT) - Daily images of each treatment field to confirm patient positioning are taken to make sure the target is in the field. This allows better targeting of the tumor and helps reduce damage to healthy tissue. Stereotactic Radiation Therapy (SRT) - This treatment delivers a large, precise radiation therapy dose to a small tumor area. SRT is often given as a single treatment or in lesser than 10 treatments.

Image-Guided Radiation Therapy (IGRT) - Daily images of each treatment field to confirm patient positioning are taken to make sure the target is in the field. This allows better targeting of the tumor and helps reduce damage to healthy tissue. Stereotactic Radiation Therapy (SRT) - This treatment delivers a large, precise radiation therapy dose to a small tumor area. SRT is often given as a single treatment or in lesser than 10 treatments. Internal radiation therapy is also called brachytherapy. In this type of radiation therapy, radioactive material is placed into cancer or surrounding tissue. Types of internal radiation therapy include: Permanent Implants - These are tiny steel seeds about the size of a grain of rice that contains radioactive material. They deliver most of the radiation therapy around the implant area. Some radiation may exit the patient’s body and thus requires safety measures to protect others from radiation exposure. Temporary Internal Radiation Therapy - Radiation therapy is given via needles, catheters, and special applicators. The radiation stays in the body from a few minutes to a few days. Most people receive radiation therapy for just a few minutes, some may receive for more time. Side effects of radiotherapy are classified as acute (early), consequential, or late effects on normal tissues over time. Acute radiation toxicity is seen within a few weeks after treatment and usually involves intermitotic cells (skin and mucosa). Consequential effects are seen when acute complications are not treated and cause persistent damage.[4] Late complications emerge months to years after exposure and usually involve postmitotic cells (liver, kidney, heart, muscle, and bone). This chapter briefly outlines a review of common complications of radiotherapy.

Radiotherapy is the single most effective non-surgical treatment of cancer.[33] In terms of overall cost, radiotherapy consumes only 5% of total spending for cancer care while forming a significant part of the treatment plan for almost 40% of patients and is responsible for a cure in about 16%.[33] There has been huge progress in the field to improve effectiveness and minimize side effects. Some techniques that can be used to reduce side effects are: Stereotactic Surgery (SRS) and Stereotactic Body Radiation Therapy (SBRT): Single fraction treatment (SRS) or multifunctional (SBRT) administration of high dose radiation to particular target areas from multiple directions to maximize dose delivery at highly specific points helps reduce exposure to surrounding normal tissues. Commonly utilized in intracranial, spinal, or extracranial sites in sensitive tissues (e.g., lungs, pancreas, head and neck cancers). Brachytherapy: Radiation source is placed inside the tissue or next to the target area and slowly emits radiation, which is active only for a short distance. Commonly utilized for prostate cancer and gynecological malignancies. Fractionation: Delivers radiation in multiple fractions allows time for normal tissues to repair before the next dose of radiation. Experimental evidence suggests that fraction size is the dominant factor in determining late effects.[13] Therefore, hyperfractionated radiotherapy - where the number of fractions is increased, and the dose per session is reduced can reduce late complications without affecting local tumor control. Image-Guided Radiotherapy and Intensity-Modulated Radiation Therapy: Utilizes real-time imaging for precise sculpting of dose distribution to guide external beam therapy to avoid irradiation of sensitive tissues deliberately. Targeted Radionuclide Therapy: Employs radionuclides that decay within the body at target tissues without accumulating in the normal tissues. Examples include radioisotopes of Iodine 131 for thyroid cancer treatment, Radium-223 for bone metastases, radionuclide linked anti-CD20 monoclonal antibodies for leukemia, lymphomas, and radionuclides embedded in resin microspheres for direct intraarterial embolization of tumors in use of liver cancers.

Targeted Radionuclide Therapy: Employs radionuclides that decay within the body at target tissues without accumulating in the normal tissues. Examples include radioisotopes of Iodine 131 for thyroid cancer treatment, Radium-223 for bone metastases, radionuclide linked anti-CD20 monoclonal antibodies for leukemia, lymphomas, and radionuclides embedded in resin microspheres for direct intraarterial embolization of tumors in use of liver cancers. Intra-Operative Radiation Therapy: Intraoperative delivery of high dose targeted radiation therapy based on clinical and frozen-section pathology results to identify areas at increased risk of local recurrence with appropriate shielding maximizes the dose of radiation to target tissue and limits exposure to surrounding normal tissues. Modification of techniques of therapeutic irradiation can play an essential role in reducing complications and enhancing local tumor control. Careful planning for radiotherapy considers likely patterns of locoregional tumor spread, uncertainties in positioning the patient for each treatment, tumor and organ movement during therapy and between treatment, tumor, and local tissue sensitivity helps to determine the appropriate irradiation dose, treatment intervals, and technique. Combined chemoradiation leads to prolonged mucosal, gastrointestinal, and urinary toxicities.[11] Acute toxicity can be mitigated by fractionation, reduction in a dose per fraction, the increasing gap between fractions and use of radioprotectors, and growth factors in the acute phase, while chronic side effects can be minimized by decreasing exposure to radiosensitive tissues. The use of appropriate tools to classify and measure toxicities can help guide treatment strategies and guidelines for radiotherapy in individual cancer treatments. Identify patients at a higher risk of radiation toxicity- e.g., patients with active collagen vascular disease, inflammatory bowel disease, and atherosclerotic vascular diseases. Use of predictive factors of clinical radiosensitivity - e.g., age, BMI.[34] Cancer-specific predictive biomarkers may help identify individual curves or subsets to determine the appropriate dosing regimen.[35][36]

Identify patients at a higher risk of radiation toxicity- e.g., patients with active collagen vascular disease, inflammatory bowel disease, and atherosclerotic vascular diseases. Use of predictive factors of clinical radiosensitivity - e.g., age, BMI.[34] Cancer-specific predictive biomarkers may help identify individual curves or subsets to determine the appropriate dosing regimen.[35][36] Coordination of care by a surgical and medical oncologist, pathologist, radiotherapist, and interdisciplinary care team consisting of oncology and radiotherapy trained nurses and PCAs, psychiatrists, neurologists, pharmacists, nutritionists, and pain management services to make an individualized patient-centered care plan can significantly reduce toxicity and improve long term quality of life for cancer survivors.

Nursing interventions and patient education play an essential role in reducing the side effects of radiotherapy. Specific strategies that can be useful include: Identification of patients at risk of complications and initiation of appropriate therapy (low BMI increases the risk of diarrhea while high BMI patients are at greater risk of skin and mucosal complications).[37][38] Oral hygiene instruction for all patients receiving head and neck irradiation. Consultation with a dentist and treatment of periodontal disease before radiotherapy can minimize the risk of jaw osteoradionecrosis. Use of bland rinses, cryotherapy, mucosal protective agents, antiseptic mouthwashes, topical analgesics, and anti-inflammatory agents or growth factors as necessary. Regular assessment and monitoring of high-risk patients can reduce long-term sequela in these patients and improve the overall quality of life. Dietary modifications that alleviate symptoms include avoiding spicy or acidic foods, caffeine, alcoholic beverages, alcohol-containing mouthwashes, and sharp foods (e.g., chips, popcorn). Nutritional assessment and dietary consult can improve the healing of damaged tissues. It is especially important in patients with cancer cachexia compounded by radiotherapy-associated fatigue, loss of appetite, alterations in taste sensations, and mucositis. Wound care interventions for skin ulcers with hydrocolloid dressings and regular cleaning and hyperbaric oxygen therapy for refractory cases. The use of probiotics reduces radiation enteritis symptoms, and dietary modifications such as a low-residue diet with no grease, spices, and adequate fiber intake can reduce symptoms of proctitis. Vaginitis douches with dilute hydrogen peroxide use for cleaning and prevention of infection following pelvic irradiation. Smoking cessation is a critical intervention to reduce the risk of secondary lung cancer in patients who receive mediastinal radiotherapy for Hodgkin disease. Some studies suggest up to a 20-fold increase in risk compared to non-smokers.