Radiation Esophagitis: Causes, Pathophysiology, Clinical Features, Imaging, and Management

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Introduction

Radiation therapy remains a cornerstone of cancer treatment for thoracic malignancies, particularly those involving the lungs, mediastinum, and thoracic spine. However, one of the most clinically significant complications is radiation-induced esophagitis, a condition that can profoundly affect patient quality of life and treatment continuity. This article explores the etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment strategies, prognosis, and includes figure references and quiz questions to optimize learning. 

Cause and Etiology

Radiation esophagitis results from the direct cytotoxic effects of ionizing radiation on the esophageal mucosa. Patients undergoing external beam radiotherapy for lung, mediastinal, or spinal malignancies are at the highest risk. The risk correlates with:

  • Radiation Dose:

    • 4500–6000 rad: High doses may result in severe, irreversible esophagitis with strictures.

    • 2000–4500 rad: Moderate doses may lead to reversible, self-limiting inflammation.

  • Chemotherapy Synergy:

    • Drugs such as doxorubicin (Adriamycin) potentiate radiation toxicity, even at relatively low radiation doses (~500 rad).

  • Radiation Field and Fractionation: Larger radiation fields and higher fraction doses increase the risk.

Pathophysiology

The esophageal mucosa is highly proliferative, making it particularly sensitive to radiation-induced injury. Key mechanisms include:

  • Acute Phase (first 2 weeks):

    • Direct DNA damage leads to apoptosis and mucosal sloughing.

    • Inflammatory cascades release cytokines (TNF-α, IL-6), leading to edema and ulceration.

  • Chronic Phase (months later):

    • Progressive submucosal fibrosis and vascular damage cause thickening and rigidity.

    • Severe damage can result in deep ulcers, tracheoesophageal (TE) fistulas, or esophageal perforation.

Epidemiology

  • Most common in patients receiving thoracic radiation for lung cancer.

  • Reported incidence varies widely, 13–37% depending on dose, chemotherapy use, and patient comorbidities.

  • Chronic radiation esophagitis with strictures typically appears 4–8 months after therapy.

  • Left main bronchus involvement is the most frequent site for fistula formation.

Clinical Presentation

Symptoms generally begin within 2 weeks of initiating radiation therapy and include:

  • Substernal burning pain

  • Odynophagia (painful swallowing)

  • Dysphagia (difficulty swallowing)

  • Weight loss from reduced oral intake

In severe chronic disease:

  • Development of strictures → progressive dysphagia

  • Tracheoesophageal fistulas → recurrent aspiration and pneumonia

  • Perforation → mediastinitis, a life-threatening complication

Imaging Features

Acute Findings (7–10 days post-radiation):

  • Double-contrast esophagography shows superficial esophageal ulcerations with irregular barium collection (Figure 1).

Chronic Findings:

  • Smooth, tapered strictures in the mid- or upper esophagus.

  • Irregular serrated mucosal contour due to ulceration and mucosal sloughing.

  • Fistula formation, most frequently to the left main bronchus, may be seen.

Figure 1. Radiation-induced inflammation of the esophagus following thoracic radiotherapy.


Treatment

Management of radiation esophagitis is supportive and symptom-driven:

  • Acute Phase:

    • Dietary modification (soft or liquid diet)

    • Viscous lidocaine, proton pump inhibitors (PPIs), and sucralfate

    • Adequate hydration and nutritional support

    • Opioid analgesia for severe pain

  • Chronic Complications:

    • Endoscopic dilation for strictures

    • Stent placement for severe or recurrent narrowing

    • Surgical repair for fistulas or perforations

    • Discontinuation or modification of chemotherapy and radiation dosage when necessary

Prognosis

  • Acute radiation esophagitis: Usually self-limiting, resolving within weeks after cessation of therapy.

  • Chronic radiation esophagitis: Carries a poorer prognosis, especially with stricture formation, recurrent fistulas, or perforation.

  • Early recognition and management improve long-term outcomes.

Quiz

1. What radiation dose range is typically associated with reversible, self-limiting esophagitis?

A) 500–1000 rad

B) 2000–4500 rad

C) 4500–6000 rad

D) >7000 rad

2. Which chemotherapy drug enhances the risk of radiation esophagitis, even at lower radiation doses?

A) Cisplatin

B) 5-Fluorouracil

C) Doxorubicin (Adriamycin)

D) Methotrexate

3. The most common site for tracheoesophageal fistula formation in chronic radiation esophagitis is:

A) Right main bronchus

B) Left main bronchus

C) Distal esophagus

D) Gastroesophageal junction

Answer & Explanation

1. Answer: B) 2000–4500 rad. Explanation: This range usually causes self-limiting mucosal inflammation, while higher doses can induce irreversible strictures.

2. Answer: C) Doxorubicin (Adriamycin). Explanation: Doxorubicin synergizes with radiation, enhancing esophageal toxicity.

3. Answer: B) Left main bronchus. Explanation: Chronic radiation-induced ulceration and necrosis often lead to fistulization, with the left main bronchus being the most common site.

Conclusion

Radiation esophagitis represents a significant dose-limiting toxicity in thoracic radiotherapy. Understanding its etiology, clinical features, imaging findings, and treatment options is crucial for optimizing cancer therapy while minimizing morbidity. With the integration of advanced radiation delivery techniques (IMRT, proton therapy), the incidence of severe complications is expected to decrease. However, vigilant monitoring and early intervention remain vital to improving patient outcomes.

References

[1] R. S. Minsky et al., "Radiation-induced esophagitis: Clinical and radiographic features," International Journal of Radiation Oncology, vol. 28, no. 4, pp. 657–662, 1994.
[2] J. C. Cox, "Toxicity of thoracic radiotherapy," Seminars in Radiation Oncology, vol. 4, no. 2, pp. 92–100, 1995.
[3] M. A. Rubenstein, "Esophageal injury from radiation and chemotherapy," Gastroenterology Clinics of North America, vol. 24, no. 3, pp. 503–520, 1995.
[4] E. R. Marks et al., "Radiation tolerance of normal tissue," Semin Radiat Oncol, vol. 5, pp. 68–81, 1995.
[5] A. Cheng and K. S. Lee, "Esophageal stricture and fistula after chemoradiation," Chest Journal, vol. 117, no. 2, pp. 317–323, 2000.
[6] Document reference: Radiation Esophagitis (방사선 식도염), Clinical Findings and Radiologic Features, 1.docx, 2025.
[7] D. Werner-Wasik et al., "Radiation-induced esophageal toxicity in lung cancer," Journal of Clinical Oncology, vol. 17, no. 10, pp. 3206–3212, 1999.

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