Esophageal Ulceration Induced by Intracavitary Irradiation for Esophageal Carcinoma
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1 269 Yoshio Hishikawa1 Shinichi Tanaka Takashi Miura Received January 23, 1984; accepted after revision April All authors: Department of Radiology, Hyogo College of Medicine, 1-1, Mukogawa-cho Nishinomiya-city, Hyogo 663, Japan. Address reprint requests to V. Hishikawa. AJR 143: , August x/84/ American Roentgen Ray Society Esophageal Ulceration Induced by Intracavitary Irradiation for Esophageal Carcinoma Twenty-two patients with esophageal carcinoma had no local recurrence after external and intracavitary radiation treatment, but all developed ulcers in the field of intracavitary irradiation. Ten were linear ulcers that appeared 3-12 months after radiation treatment (mean, 5.3 months); the other 12 were the long circumferential type and appeared 1-8 months after irradiation (mean, 3.7 months). Esophagobronchial fistulae developed in two cases in which deep ulcer had been found between the completion of external irradiation and the beginning of intracavitary irradiation. In these cases with deep ulcer, intracavitary irradiation should not be done. For patients receiving intracavitary radiation, the total dosage should be less than 2 Gy. Prognosis of esophageal carcinoma treated by external irradiation alone is rather poor because of local recurrence and distant metastasis [1 1]. Recently intracavitary irnidiation has been used as a boost therapy after external irradiation to obtain better local control [2-6]. In our department, since May 198, patients with esophageal cancers have been treated by a high dose rate, remote-controlled afterloading unit as boost therapy of intracavitary irradiation after external irradiation. Local control rate at 1 year was 62.1 %, which was significantly better than 1 8.% of the group treated with external irradiation alone [7]. However, esophageal ulcers were found as complications in 22 (95.7%) of 23 patients who had no local recurrence after radiotherapy. We describe these ulcers. Subjects and Methods Between May 1 98 and March 1983, 31 cases of esophageal carcinoma were primarily treated by a high dose rate, remote-controlled afterloading unit as boost therapy after the completion of external irradiation at the Department of Radiology at the Hospital of Hyogo College of Medicine. After radiotherapy, benign ulcers werefound in 22 patients and malignant ulcers in six patients. Endoscopic biopsy of all 22 benign ulcers proved that there was no local recurrence. Another two patients had malignant stricture, and the last one had neither local recurrence nor benign ulcer. All cases underwent barium esophagography and endoscopy after radiotherapy. During the first 6 months, these examinations were performed every month. Results Through our examinations, we have noted the differences in radiographic features between malignant and benign ulcers. All six malignant ulcers were surrounded by a thick crater wall and four of them showed irregularity in the ulceration. In sharp contrast, only two (9.1 %) of the 22 benign ulcers were surrounded by a thick crater wall and three (1 3.6%) showed irregularity in the ulceration. All the benign ulcers appeared in the field of intracavitary irradiation, whereas no ulcer was found in the field of external irradiation alone (fig. 1). Ten cases were linear ulcer, one of which developed a esophagobronchial fistula,
2 27 HISHIKAWA ET AL. AJR:143, August 1984 A B Fig year-old man. A, Field of intracavitary irradiation. Patient died from liver metastasis 2 years and 1 month after radiotherapy. B, Autopsy specimen. Long circumferential ulcer (between arrowheads) in field of both external and intracavitary irradiation, but only mucosal change without ulceration (between arrows) in field of external irradiation alone. A B C Fig year-old man. A and B, 7 months after radiotherapy. Linear ulcer (arrows) on anterior wall. C, 12 months after radiotherapy. Linear ulcer healed by conservative treatment.
3 AJR:143, August 1984 RADIATION-INDUCED ESOPHAGEAL ULCERS 271 Fig year-old man. A, 6-cm-long spiral-type carcinoma in mid esoph- almost smooth. C, 5 months after radiotherapy. Long circumferential ulcer in agus before radiotherapy. B, 2 weeks after effective radiotherapy (external field of intracavitary irradiation., 1 months after radiotherapy. Long circurnirradiation of 5 Gy plus intracavitary irradiation of 12 Gy). Esophageal wall ferential ulcer almost healed. and 1 2 were long, circumferential ulcers, one of which also developed a esophagobronchial fistula. Linear ulcers were identified months after radiotherapy (mean, 5.3 months), and long, circumferential ulcers at 1-8 months (mean, 3.7 months). On the esophagram, a linear ulcer appears in profile as a long, linear protrusion of the wall and en face as a linear fleck of barium (fig. 2). A long, circumferential ulcer appears as long, rigid mucosal change on double contrast (fig. 3). In the two cases of fistula, deep ulcer was shown between the administration of external irradiation and intracavitary irradiation (fig. 4). Figure 5 shows the correlation between the delivered dosage and the types of ulcer. Seven cases receiving 2 Gy or more of intracavitary irradiation were circumferential ulcers with deep mucosal defect, and one of them developed fistula. Three cases receiving 1 Gy or less of intracavitary irradiation were linear ulcers. The patient who had neither local recurrence nor benign ulcer was given only 6 Gy of intracavitary irradiation. Linear ulcers were cured to become a scar by conservative treatment of 4-6 months. Long, circumferential ulcers were more difficult to cure. Discussion Ulcers of the normal esophagus induced by radiation treatment are not very common [8, 9]; however, it has been reported that radiotherapy combined with chemotherapy can damage the esophagus more easily [1 -i 2]. In our series, all cases were treated with external and intracavitary irradiation without chemotherapy. Diagnosis of esophageal ulcer is made by esophagoscopy and esophagography. When an esophageal ulcer is found, it first must be identified as malignant or benign. Roswit [13] reported difficulty in distinguishing between radiation alteration and recurrent cancer. The radiation-induced lesion is smooth and tapering, whereas the recurrent lesion has an irregular defect with surrounding overhanging edges [8, 13]. In our series, similar differences were observed between malignant and benign ulcers. Among benign ulcers, the linear ulcer cannot be detected easily by esophagography; however, it is more easily detected by endoscopy. Lepke and Libshitz [9] reported that radiation-induced ulcer did not develop in a uniform time frame. Their treatment was external irradiation alone. In our series, in which external and intracavitary irradiation were combined, linear ulcers were seen 3-12 months after radiotherapy (mean, 5.3 months), and long, circumferential ulcers were seen at 1-8 months (mean, 3.7 months). According to Northway et al. [1 4] in their experiments on opossums, esophagitis after external irradiation proved doserelated, and barium esophagography at 1 week showed ulceration when the delivered dose exceeded 22.5 Gy. In the treatment of humans, the tolerance dose to prevent chronic
4 272 HISHIKAWA ET AL. AJR:143, August 1984 A B C C x Ui Gy oo (. +. Fig year-old rnan. A, After completion of external irradiation of 4 Gy. Deep ulcer on posterior wall of esophagus. B, After completion of intracavitary irradiation of 24 Gy. Esophageal wall still irregular. C, 6 months after intracavitary irradiation, esophageal fistula appeared. Endoscopy performed at 5 months had shown long circumferential necrotic ulceration. Biopsy revealed only necrotic tissues and no cancer cells. Patient died; autopsy was not performed. injury to the esophagus seems to be around 6 Gy, given at a rate of 1 Gy/week by external irradiation [1 5]. We found in our treatment that formation of ulcers correlated with the dosage of intracavitary irradiation, which delivers additional dosage after the completion of external irradiation. When esophageal carcinoma is treated with intracavitary irradiation, the question is always the appropriate dosage to be delivered. Although better local control can be achieved by a higher dosage of intracavitary irradiation, the higher dosage causes more severe esophageal injury. From the results of this series and those from our earlier report [7], we recommend the total dosage be less than 2 Gy for intracavitary irradiation. Contraindications to intracavitary irradiation are the cases that developed deep ulcer after external irradiation. Therefore, cases with deep ulcer no longer undergo intracavitary irradiation at our department. As long ago as 1 925, Guisez [1 6] had reported this contraindication of intracavitary irradiation. Ulcer induced by intracavitary irradiation is a serious problem, but cases without fistula can be cured by conservative treatment. Consequently, intracavitary irradiation of esophageal carcinoma as boost therapy should be more highly recommended for obtaining better local control. Intracavitary Gy REFERENCES Irradiation Fig. 5.-Correlation of dosage and ulcer type. Open circle = linear ulcer; solid circle = long circumferential ulcer; cross = fistula. 1. Pearson JG. The value of radiotherapy in the management of esophageal cancer. AJR 1969;1 5: Rider WD, Mendoza RD. Some opinions on treatment of cancer
5 AJR:143, August 1984 RADIATION-INDUCED ESOPHAGEAL ULCERS 273 of the esophagus. AJR 1969;15: Nishio M, Sakurai T, Sakawa K, et al. Intracavitary radium therapy combined with external irradiation for the treatment of esophageal cancer. Jpn J Cancer Clin 1978;24: 199-i Bottnll DO, Plane JH, Newaishy GA. A proposed afterloading technique for irradiation of the oesophagus. Br J Radiol 1979;52: George FW Ill. Radiation management in esophageal cancer: with a review of intraesophageal radioactive iridium treatment in 24 patients. Am J Surg 198;139: Moorthy CR, Nibhanupudy JR. Ashayeri E, et al. Intraluminal radiation for esophageal cancer: a Howard University technique. J NatI Med Assoc 1982;74: Hishikawa Y. Radiation treatment of esophageal carcinoma using a high-dose-rate remote afterloader. Radiat Med 1983;1 : Rubin P. The radiographic expression of radiotherapeutic injury: an overview. Semin Roentgenol 1974;9: Lepke RA, Libshitz HI. Radiation-induced injury of the esophagus. Radiology 1983;148: Greco FA, Brereton HD, Kent H, Zimbler H, Merrill J, Johnson RE. Adriamycin and enhanced radiation reaction in normal esophagus and skin. Ann Intern Med 1976;85: Newburger PE, Cassady JR, Jaffe N. Esophagitis due to adriamycin and radiation therapy for childhood malignancy. Cancer 1978;42: Boal DKB, Newburger PE, Teele RL. Esophagitis induced by combined radiation and Adriamycin. AJR 1979;1 32 : Roswit B. Complications of radiation therapy: the alimentary tract. Semin Roentgenol 1974;9: Northway MG, Ubshitz HI, West JJ, et al. The opossum as an animal model for studying radiation esophagitis. Radiology 1979;131 : Seaman WB, Ackerman LV. The effect of radiation on the esophagus: a clinical and histologic study of the effects produced by the Betatron. Radiology 1957;68: Guisez J. Malignant tumors of the esophagus. J Laryngol Otol 1925;4:
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