Abstract
Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40–50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity. Treatment with a prostaglandin inhibitor, naproxen, was not protective. Esophagitis may be complicated by esophageal candidiasis, but its contribution to the patient's morbidity is unclear.
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References
Emami B, Perez C: Carcinoma of the lung.In Principles and Practice of Radiation Oncology. CA Perez, LW Brady (eds). Philadelphia, JB Lippincott, 1987, pp 680–683
Rubin P, Casarrett GW: Alimentary canal: esophagus and stomach.In Clinical Radiation Pathology, Vol 1. Philadelphia, WB Saunders, 1968, pp 153–192
Seaman WB, Ackerman LV: The effects of irradiation on the esophagus. A clinical and histological study of the effects produced by the betatron. Radiology 68:534, 1957
Hahn GL, Menconi MJ, Cahill M, Polgar P: The influence of gamma radiation on arachidonic acid release and prostacyclin synthesis. Prostaglandins 25:783–791, 1983
Dubois A, Dorval ED, Steel L, Piala NP, Conklin JJ: Effect of ionizing radiation on prostaglandins and gastric secretion in rhesus monkeys. Radiat Res 110:289–293, 1982
Summers RW, Glenn CE, Flatt AJ, Elahmady A: Radiation and indomethacin effects on morphology, prostaglandins, and motility in dog jejunum. Am J Physiol 261:G145–151, 1991
Tanner NSB, Stamford IF, Bennett A: Plasma prostaglandins in mucositis due to radiotherapy and chemotherapy for head and neck cancer. Br J Cancer 43:767–771, 1981
Gal D, Strickland DM, Lifshitz S, Buchsbaum HJ, Mitchell MD: Effect of radiation on prostaglandin production by human bowelin vitro. Int J Radiat Oncol Biol Phys 10:653–657, 1984
Northway MG, Libshitz HI, Osborne BM, Feldman MS, Mamel JJ, West JH, Szwarc IA: Radiation esophagitis in the opossum: Radioprotection with indomethacin. Gastroenterology 78:883–892, 1980
Tochner Z, Barnes M, Mitchell JB, Orr K, Glatstein E, Russo A: Protection by indomethacin against acute radiation esophagitis. Digestion 47:81–87, 1990
Nicolopoulos N, Mantidis A, Stathopoulos E, Papaodysseas S, Kouvaris J, Varveris H, Papavasiliou C: Prophylactic administration of indomethacin for irradiation esophagitis. Radiother Oncol 3:23–25, 1985
Savary M, Miller G: The Esophagus. Handbook and Atlas of Endoscopy. Solothurn, Switzerland, Gassman, 1978
Hamilton SR: Reflux esophagitis and Barrett esophagus.In Gastrointestinal Pathology. H. Goldman, HD Appelman, N Kaufman (eds). Baltimore, Williams and Wilkins, 1990, pp 11–68
Kodsi BE, Wickremesinghe PC, Kozinn PJ, Kadirawelpillai I, Goldberg PK:Candida esophagitis: A prospective study of 27 cases. Gastroenterology 71:715, 1976
Woolson RF: Stat Methods for the Analysis of Biomedical Data. New York, Wiley, 1987, p 488
Berthrong M, Fajardo LF: Radiation injury in surgical pathology. Part II. Alimentary tract. Am J Surg Pathol 5:153, 1981
McCraken JD, Janaki LM, Taylor SB, Shankar Giri PG, Weiss GB, Gordon W Jr Vance RB, Crowley J: Concurrent chemotherapy and radiotherapy for limited small cell carcinoma of the lung. A southwest oncology group study. Semin Oncol 13:31–36, 1986
Corder MP, Tewfik HH, Clamon GH, Platz CE, Leimert J, Herbst KD, Byfield JE: Radiotherapy plus razoxane for advanced limited extent carcinoma of the lung. Cancer 53:1852–1856, 1984
Marks JE, Moran EM, Griem ML, Ultmann JE: Extended mantle radiotherapy in Hodgkin's disease and malignant lymphoma. AJR 121:772–788, 1974
Mascarenhas F, Silvestre ME, Sa da Costa M, Grima N, Campos C, Chaves P: Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung. Am J Clin Oncol 12:34–40, 1989
Vanagunas A, Jacob P, Olinger E: Radiation induced esophageal injury: A spectrum from esophagitis to cancer. Am J Gastroenterol 85:808–812, 1990
Chen TY, Webster JH: OralMonilia. Study on patients with head and neck cancer during radiotherapy. Cancer 34:246–249, 1974
Poland JM: The role ofCandida injections as an adverse effect upon head and neck cancer patients undergoing therapeutic radiation and the effect of antimycotic treatment. Mycoses 32(suppl 2):39–41, 1989
Lepke RA, Libshitz HI: Radiation-induced injury of the esophagus. Radiology 148:375–378, 1983
Goldstein HM, Rogers LF, Fletcher GH, Dodd GD: Radiological manifestation of radiation-induced injury to the normal upper gastrointestinal tract. Radiology 117:135–140, 1975
Willoughby DA, Girond JP, DiRosa M, Velo GP: The control of inflammatory response with special reference to prostaglandins.In Prostaglandins and Cyclic AMP: Biological Actions and Clinical Applications. RH Kahn, WEM Lands (eds). New York, Academic Press, 1973, pp 187–206
Northway MG, Bennett A, Carroll M: Comparative effects of anti-inflammatory agents and radiotherapy on normal esophagus and tumors in animals. Gastroenterology 78:A1229, 1980
Zacharski LR, Constantini V, Moritz TE, Haakenson CM: Chronic nonsteroidal antiinflammatory drug use in a cohort of patients with advanced lung and colon cancer.In Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury. KV Honn, LJ Marnett, S Nigam, T Walden (eds). New York, Kluwer Academic Publishers, 1991, pp 497–501
Fleis JL: Statistical Methods for Rates and Proportions, 2nd ed. New York, Wiley, 1981
Ambrus JL, Johnson R, Nava H, Lillie DB, Laasptar H: Experimental and clinical studies on reducing radiation therapy induced esophagitis and cystitis. Proc Annu Meet Am Assoc Cancer Res 25:202, 1984
Hupp EW, Hajibeigi A, Hardcastle JE: Leukotriene production by gamma irradiated macrophage cells.In Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury. KV Honn, LJ Marnett, S Nigam, T Walden (eds). New York, Kluwer Academic Publishers, 1991, pp 161–164
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Soffer, E.E., Mitros, F., Fred Doornbos, J. et al. Morphology and pathology of radiation-induced esophagitis. Digest Dis Sci 39, 655–660 (1994). https://doi.org/10.1007/BF02088356
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DOI: https://doi.org/10.1007/BF02088356