Continue Reading

Current and Potential Treatments

Grade 2 esophagitis is treated with oral dietary supplements; grade 3 usually requires hospitalization and tubal feeding or total parenteral nutrition.3Diagnostic imaging plays an increasingly important role in quantifying, characterizing, and grading radiation esophagitis.5

Experimental treatments for ARIE currently undergoing clinical testing include manuka tree honey (ClinicalTrials.gov identifier: NCT01262560), oral epigallocatechin-3-gallate (EGCG6; ClinicalTrials.gov identifier: NCT02577393), glutamine (ClinicalTrials.gov identifier: NCT01952847), and doxepin hydrochloride (ClinicalTrials.gov identifier: NCT02062632). Investigational radioprotective agents such as amifostine have been studied as preventive agents but have not been shown to be protective against high-grade radiation esophagitis.3

Low-grade esophagitis is currently managed with analgesics and anesthetics such as benzocaine, antiviral and antibacterial agents, anti-inflammatory corticosteroids, acid suppression (eg, ATPase inhibitors such as omeprazole) — and importantly, dietary change.1-3Anorexia is a common complication of ARIE; referring patients with ARIE to a nutritionist can help patients maintain nutrition despite painful or difficult swallowing.1-3Severe cases are typically treated with endoscopic dilatation or surgery, but can persist even after these invasive interventions.3

Clinical and radiographic scoring systems can objectively quantify the severity of ARIE and late-radiation esophagitis and efforts are underway to scientifically evaluate the reliability of patient self-report-based scoring systems. For example, computed tomography (CT) scans can be used to help grade ARIE severity.5

However, development of more strongly predictive biomarkers and models are urgently needed to reliably identify those patients who face the highest risk of experiencing ARIE or late radiation esophagitis.7-12Metabolic or functional imaging with 18F-fluorodeoxyglucose positron emission tomography (FDG PET) can be used to detect early esophageal changes that are predictive of high grade (grade 3) ARIE 2 weeks after initiation of radiotherapy.7

Predicting Radiation Esophagitis

Accurately predicting radiation esophagitis and odynophagia is an important goal for patient risk stratification, treatment planning, monitoring, and timely interventions. Currently, however, there are no definitive, universally employed systems for doing so.

Women, white patients, patients with existing gastroesophageal reflux or poor baseline performance status, and low body mass index (BMI) are at greater risk of developing severe ARIE than are other patients.3The role of age in radiation esophagitis risk is less clear; it was long believed that elderly patients (70 years or older) are at increased risk of ARIE, but recent studies suggest a lowerincidence among elderly patients.3,13

Radiation dose to esophageal mucosa and other esophagus tissues is a well-established risk factor for ARIE. Esophageal radiation dose is predictive of ARIE; mean whole-esophagus dose less than 34 Gy is associated with up to 20% incidence of grade 3 or higher radiation esophagitis, and there is also evidence that the proportion or percentage of the esophageal mucosa receiving more than 50 Gy total radiation dose is predictive of radiation esophagitis.3However, there is not yet consensus about the optimal dosimetric prediction.3

Dose-based risk prediction is strengthened when included in multivariate statistical models alongside biomarkers such as baseline levels of inflammatory cytokines (eg, interleukin 8 [IL-8]).1-3,8-12Elevated serum levels of certain non-gene-coding micro-RNAs at 2 weeks after treatment begins might also predict severe ARIE.14

But until large, randomized prospective validation trials are conducted, these biomarkers and multivariate models will remain investigational. 

References

1. Murro D, Jakate S. Radiation esophagitisArch Pathol Lab Med.2015;139(6):827-830.

2. Chiu N, Pulenzas N, Maranzano E, et al. Chapter 7. GI symptoms: radiation-induced adverse events. In: Krishnan MS, Racsa M, Yu HHM (eds). Handbook of Supportive and Palliative Radiation Oncology.London, UK: Academic Press. 2017:85-100.

3. Baker S, Fairchild A. Radiation-induced esophagitis in lung cancerLung Cancer (Auckl).2016;7:119-128.

4. Shields H, Li J, Pelletier S, et al. Persistence of dysphagia and odynophagia after mediastinal radiation and chemotherapy in patients with lung cancer or lymphomaDis Esophagus.2017;30(2):1-8.

5. Niedzielski JS, Yang J, Stingo F, et al. Objectively quantifying radiation esophagitis with novel computed tomography-based metricsInt J Radiat Oncol Biol Phys.2016;94(2):384-393.

6. Zhu W, Zhao H, Chen G, et al. Oral epigallocatechin-3-gallate treats acute radiation-induced esophagitis in patients with esophageal cancer receiving chemoradiation therapy/radiation therapyInt J Radiation Oncol Biol Phys.2016;96(2 suppl):E581.

7. Mehmood Q, Sun A, Becker N, et al. Predicting radiation esophagitis using 18F-FDG PET during chemoradiotherapy for locally advanced non-small cell lung cancerJ Thorac Oncol.2016;11(2):213-221.

8. Wang S, Campbell J, Stenmark MH, et al. A model combining age, equivalent uniform dose and IL-8 may predict radiation esophagitis in patients with non-small cell lung cancerRadiother Oncol.2018;126(3):506-510.

9. Paximadis P, Schipper M, Matuszak M, et al; Michigan Radiation Oncology Quality Consortium. Dosimetric predictors for acute esophagitis during radiation therapy for lung cancer: results of a large statewide observational studyPract Radiat Oncol.2018;8(3):167-173.

10. Hawkins PG, Boonstra PS, Hobson ST, et al. Prediction of radiation esophagitis in non-small cell lung cancer using clinical factors, dosimetric parameters, and pretreatment cytokine levelsTransl Oncol.2018;11(1):102-108.

11. Tang C, Liao Z, Zhuang Y, et al. Acute phase response before treatment predicts radiation esophagitis in non-small cell lung cancerRadiother Oncol.2014;110(3):493-498.

12. Olling K, Nyeng DW, Wee L. Predicting acute odynophagia during lung cancer radiotherapy using observations derived from patient-centred nursing careTech Innov Patient Support Radiat Oncol.2018;5:16-20.

13. Soni PD, Boonstra PS, Schipper MJ, et al. Lower incidence of esophagitis in the elderly undergoing definitive radiation therapy for lung cancerJ Thorac Oncol.2017;12(3):539-546.

14. Xu T, Liao Z, O’Reilly MS, et al. Serum inflammatory miRNAs predict radiation esophagitis in patients receiving definitive radiochemotherapy for non-small cell lung cancerRadiother Oncol.2014;113(3):379-384.