Radiation Esophagitis


Article Author:
Zeid Nesheiwat


Article Editor:
Kunal Mahajan


Editors In Chief:
Ishwarlal Jialal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/9/2019 10:06:27 PM

Introduction

Radiation esophagitis is inflammation of the esophagitis due to radiation. Radiation esophagitis is typically an adverse effect that develops in individuals receiving radiation cancer therapy, most commonly for breast, lung, and other lymphomas. Symptoms present two to three weeks after initial therapy and include throat pain, dysphagia, and the sensation that food is stuck. Ethyol (amifostine) is a medication used as a radiation protector in selected populations at risk of radiation esophagitis. Typically administered via injection 30 minutes before therapy, patient studies have been promising, showing a reduced risk of developing radiation esophagitis. The goal when treating this condition is adequate nutrition intake, and it is advisable for patients to refrain from eating hot or spicy foods that can further irritate the esophageal lining. In severe cases, perforations, ulcerations, dysmotility, and tracheoesophageal fistulas can be seen. Although there is no cure for radiation esophagitis, symptoms regress 2 to 4 weeks after the completion of radiation treatment.[1][2][3]

Etiology

Radiation esophagitis is inflammation, edema, erythema, and erosion of the mucosal surface of the esophagus caused by radiation therapy to nearby or related structures that cause cell damage, produce proinflammatory cytokines, and lead to the development of free-oxygen radical species related to radiation therapy. 

Epidemiology

Radiation esophagitis is an adverse effect for patients undergoing radiation cancer therapy, usually for lung, breast, and other thoracic cancers due to its proximity. Symptomatic radiation esophagitis, however, is a rare complication of radiation therapy affecting the minority of patients undergoing treatment. In addition, genetics have been thought to play an important role in a patient who develops radiation esophagitis, with some research correlating single-nucleotide polymorphisms of transforming growth factor b-1 with severe radiation esophagitis.[4][5]

Pathophysiology

Radiation therapy leads to mucosal damage, production of pro-inflammatory cytokines, and eventually cell death which leads to ulcerations of the esophageal mucosal lining. Radiation therapy causes cell DNA damage, leading to stress-related, pro-inflammatory cytokine production through various signaling pathways and ultimately causing mucosal damage and irritation. If severe, ulcerations of the mucosal wall can occur.

Histopathology

Endoscopy in the acute setting may reveal erythema, erosion, mucosal soughing, ulcerations, and hemorrhage. In the chronic setting, fibrosis, atypia, and chronic inflammatory changes may be seen.

Effects of radiation esophagitis predominately involve the basal cells of the squamous epithelium. Within 48 hours of radiation therapy, apoptotic bodies are seen. Within a few weeks, the submucosal layers of the esophagus become involved with mucosal gland degeneration, endothelial swelling, and capillary dilation creating erythema. Within one month, cytological atypia is described as having irregular nuclear membranes and abnormal smudge nuclei with loss of detail with prominent nuclei. In addition, the cytoplasm will reveal a bubble appearance, pleomorphism, cytomegaly, and hyperchromic nuclei with other common findings including parakeratosis and mucosal atrophy.

In chronic esophagitis, fibroblasts and inflammatory cells infiltrate the muscle wall, leading to edema, and thickening of the submucosa, leading to fibrosis and stricture formation.

History and Physical

Certain risk factors may predispose patients to a high risk of developing radiation esophagitis. These include Caucasian race, age greater than 70, female sex, poor initial performance status, low body mass index, gastroesophageal reflux disease, and dysphagia. In addition, patients with esophageal infiltrated tumors or late-stage cancer have an increased risk of radiation esophagitis.

When examining a patient with a history of cancer with radiation therapy, it is always important to ask about symptoms of the recurrent disease, i.e., weight loss, worsening respiratory status, dysphagia, or hoarseness. A physician must evaluate the oral mucosa extensively, look for signs of thrush or lesions, evaluate for lymphadenopathy, and perform a thorough respiratory exam.

Common symptoms include dysphagia, nausea, anorexia, and odynophagia.

Evaluation

Radiation esophagitis can be classified as acute or late. Acute radiation esophagitis develops less than 3 months after therapy whereas late occurrences develop greater than 3 months after therapy. However, most cases of acute radiation esophagitis develop within 2 to 3 weeks post initial treatment and 6 months for late development. Symptoms may be cumulative but are typically self-limiting. In severe causes, dysmotility, perforations, fistula, and strictures can develop.[6][7]

The diagnosis is typically made clinically in these patients; however, if there is a concern for more serious complications, further diagnostics may be needed. A barium swallow should be used to evaluate for esophageal strictures or impaired peristaltic waves and dysmotility. CT chest and abdomen may be used to evaluate for fistula and characterization of strictures. Upper endoscopy may be used to evaluate for ulcerations and biopsy if needed.

Treatment / Management

Treatment is supportive care with adequate hydration and nutrition intake. Amifostine, an organic triphosphate, has been studied and shown to act as a radioprotector. It is thought that this medication acts as an antioxidant to neutralize the free-oxygen radicals produced during ionizing radiation. A study performed to look at the effects of amifostine in patients with advanced non-small cell lung cancer showed improvement of swallowing dysfunction but no effect on reducing rates of esophagitis in severe cases. Another potential radioprotectant, glutamine, has been associated with reduced rates of esophagitis. A small prospective study in non-small cell lung cancer patients showed 49% reported no esophagitis when treated prophylactically with glutamine powder. NSAIDs and other non-steroidal have been studied but have not proven effective.[8][9][10]

Dietary modification in the form of soft, bland diets is typically used along with the removal of irritant foods such as alcohol, spicy foods, and very hot or cold foods. Frequent, small meals also help. Nutritional support may be needed, using supplements, intravenous hydration, electrolyte correction, and total parenteral nutrition. Analgesia is typically needed, using topical or systemic methods. Prophylactic antifungal therapy is indicated due to the increased risk of thrush.[11][12]

If a stricture is present, then dilatation may be required. However, complications like aspiration and perforation are also potential problems.

 There are reports of the use of stents to relieve long strictures.

Differential Diagnosis

Radiation esophagitis may develop in the acute stage of therapy or the chronic stage of therapy. Patient with severe esophagitis are at a higher risk of developing long-term complications, and physicians must be able to recognize severe life-threatening such as ulcerations, perforations, fistula, and strictures.

CMV esophagitis must be ruled out in these patients.

Staging

Grading of Radiation Esophagitis

Grade/Description

0/No symptoms

1/Mild fibrosis and difficulty with swallowing solids

2/Dysphagia-Dilatation may be required

3/Severe fibrosis, only able to swallow liquids, Dilatation is necessary

4/Necrosis, perforation or fistula formation

Complications

Although radiation esophagitis is relatively benign and self-limiting, In severe cases, it can cause ulcerations, esophageal perforations, tracheoesophageal fistula, stricture development. Severe cases have been associated with genetic factors and polymorphisms.

Postoperative and Rehabilitation Care

  • Spicy and very hot/cold foods have to be avoided
  • A soft pureed bland diet is preferred
  • A dietitian consult can help assess the daily calorie requirement.
  • Some patients may require IV hydration or tube feedings.
  • The discomfort of pain may respond to oral lidocaine, NSAIDs and PPIs.
  • Nystatin swish and swallow is highly recommended as these patients are also prone to thrush and candida esophagitis.

Consultations

In the absence of severe disease, i.e., perforation, ulceration, fistula, stricture, or severe malnutrition due to dysphagia, no consultations are needed. In cases where a procedure or endoscopic dilation is needed, consultations are appropriate.

Deterrence and Patient Education

Many agents have been studies to prevent radiation-induced esophagitis. Amifostine, L glutamine and NSAIDS have all been investigated with conflicting data. The key to prevention is awareness and obtaining a nutritional consult early in the disease.

Pearls and Other Issues

Current research has been looking at the use of granulocyte macrophage colony stimulating factor and honey to prevent radiation esophagitis.

Enhancing Healthcare Team Outcomes

Radiation esophagitis is a common problem in patients who receive upper-body radiation. The patient is often unable to eat solids and/or liquids. In addition, eating and swallowing is often associated with pain. The management of this condition is multidisciplinary. The nurse plays a vital role in educating the patient prior to radiation about this complication. Further, the nurse is responsible for monitoring the amount of food intake and weight gain/loss. The pharmacist can help lower the pain and the discomfort by providing viscous lidocaine and proton pump inhibitors/sucralfate. Because the patients are also prone to fungal esophagitis, the pharmacist must be proactive and encourage starting the patient on nystatin. Finally, the dietitian is vital as many patients may have difficulty eating. The dietitian can assess the calorie requirements and suggest alternative ways of delivering the calories.[13] (level III)

Outcomes

Despite advances in delivering radiation, esophagitis still continues to occur and carries a high morbidity. The actual outcomes of patients with radiation esophagitis are not accurately reported but the numbers are not minuscule.

However, the prognosis of radiation esophagitis is good. This disease process is an adverse effect of radiation therapy, and symptoms usually resolve within 2 to 4 weeks after radiation therapy has been completed. In some cases, with high dosage radiation, long-term complications include stricture formation or perforation. Emami et al. estimated that 5% of patients who received radiation therapy at 60 Gy developed late complications.

Patients who underwent radiation and developed radiation esophagitis have 5- to 10-fold increased risk of developing esophageal squamous cell carcinoma. Adequate long-term follow up is needed.[14] (Level III)


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Radiation Esophagitis - Questions

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Which statement is false concerning radiation-induced esophageal pathology?



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A 75-year-old female presents for follow up for multiple episodes of pneumonia. The patient has had a history of non-small cell lung cancer that has been treated with chemotherapy and radiation 15 years ago. Her only complication of treatment at that time was nausea and radiation esophagitis. What would be the next best step in her workup for her pneumonia?



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Which mucosal layer is predominantly involved in radiation esophagitis?



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Which of the following is not seen on histological evaluation of acute radiation esophagitis?



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Which is the following is not a risk factor for developing radiation esophagitis?



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What medication class is given prophylactically for patients suffering from radiation esophagitis?



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What is the best imagining modality to evaluate for esophageal strictures secondary to radiation esophagitis?



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New studies for the treatment of radiation esophagitis have focused predominantly on which colony-stimulating factor?



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Radiation Esophagitis - References

References

Agarwal V,Logie N,Morris CG,Bradley JA,Rotondo RL,Bradfield SM,Indelicato DJ, Esophagitis associated with multimodality management of pediatric Ewing sarcoma of thorax. Pediatric blood     [PubMed]
Verma V,Simone CB 2nd,Werner-Wasik M, Acute and Late Toxicities of Concurrent Chemoradiotherapy for Locally-Advanced Non-Small Cell Lung Cancer. Cancers. 2017 Sep 8     [PubMed]
Simone CB 2nd, Thoracic Radiation Normal Tissue Injury. Seminars in radiation oncology. 2017 Oct     [PubMed]
So K,Smith RE,Davis SR, Radiotherapy in anaplastic thyroid carcinoma: An Australian experience. Journal of medical imaging and radiation oncology. 2017 Apr     [PubMed]
Baker S,Fairchild A, Radiation-induced esophagitis in lung cancer. Lung Cancer (Auckland, N.Z.). 2016     [PubMed]
Gong B,Jiang N,Yan G,Wang S,Deng C,Wei S,Zhao Y, Predictors for severe acute esophagitis in lung cancer patients treated with chemoradiotherapy: a systematic review. Current medical research and opinion. 2016 Jul 20     [PubMed]
Murro D,Jakate S, Radiation esophagitis. Archives of pathology     [PubMed]
Ma L,Qiu B,Li Q,Chen L,Wang B,Hu Y,Liu M,Zhang L,Huang Y,Deng X,Xia Y,Lin M,Liu H, An esophagus-sparing technique to limit radiation esophagitis in locally advanced non-small cell lung cancer treated by simultaneous integrated boost intensity-modulated radiotherapy and concurrent chemotherapy. Radiation oncology (London, England). 2018 Jul 17     [PubMed]
Yau V,Lindsay P,Le L,Lau A,Wong O,Glick D,Bezjak A,Cho BCJ,Hope A,Sun A,Giuliani M, Low Incidence of Esophageal Toxicity After Lung Stereotactic Body Radiation Therapy: Are Current Esophageal Dose Constraints Too Conservative? International journal of radiation oncology, biology, physics. 2018 Jul 1     [PubMed]
Ravich WJ, Endoscopic Management of Benign Esophageal Strictures. Current gastroenterology reports. 2017 Aug 24     [PubMed]
Kim JW,Kim TH,Kim JH,Lee IJ, Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy. World journal of gastroenterology. 2018 Feb 21     [PubMed]
Yuce Sari S,Yazici G,Yuce D,Karabulut E,Cengiz M,Ozyigit G, The effect of glutamine and arginine-enriched nutritional support on quality of life in head and neck cancer patients treated with IMRT. Clinical nutrition ESPEN. 2016 Dec     [PubMed]
Challand T,Thureau S,Dubray B,Giraud P, [Esophageal toxicity of radiation therapy: clinical risk factors and management]. Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique. 2012 Sep     [PubMed]
Billiet C,Peeters S,De Ruysscher D, Focus on treatment complications and optimal management: radiation oncology. Translational lung cancer research. 2014 Jun     [PubMed]

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