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1 LATE COMPLICATIONS FOLLOWING IRRADIATION FOR ESOPHAGEAL CANCER \ ANALYSIS ON 5-YEAR SURVIVORS \ Masashi TSUMURA*1, Mari TASHIRO*1, Keiko HIROKAWA*1, Yoshie TAKADA*1, Mariko SAKASHITA*1, Takuhito TADA*1, Toshiyuki NISHITA*1, Toshifumi NAKAJIMA*1, Yasuto ONOYAMA*2, Haruyuki FUKUDA*1 (Received 13 February 1995, accepted 23 June 1995) Abstract Severity and frequency of late complications were investigated in long-surviving patients who had received radiotherapy for esophageal cancer from 1980 to Ten patients who had survived more than 5 years were studied. Pathologically, squamous cell carcinoma was demonstrated in all 10 patients, which involved 8 males and 2 females aged 51 to 86 years (average, 69). The exposure dose was 70 Gy/35-38fr/7-7.5w in patients with external irradiation alone and Gy/27-32fr/ w externally and 6-16Gy/2-5fr/2-3w internally in patients with external and intracavitary irradiation. Stenosis appeared from 4 to 40 months after radiotherapy in 9 of the 10 patients, and 2 patients developed fistulas. There were 4 patients with serious complications requiring surgical treatment (severe stenosis in 3 patients and fistula with lung abscess in 1 patient). For patients treated with external and intracavitary brachytherapy, the severity of late complications increased when the total dose including both external and intracavitary irradiation exceeded 70Gy. Determining an appropriate therapeutic dose for esophageal cancer is extremely difficult, and a strict, long-term follow-up procedure must be performed along with appropriate treatment. Key words: Esophageal cancer, Radiotherapy, Late complication Department of Radiology, Osaka City University Medical School (1-5-7 Asahimachi Abeno-ku, Osaka, 545 JAPAN)
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3 Table 1. Patients characteristics *Guide Lines for the Clinical and Pathological Studies on carcinoma of the Esophagus,March 1992 (8th edition) **Grade 0: no symptom and no radiologic abnomality, 1: minor symptom requiring non-surgical management 2: major symptom requiring surgical management, 3: life threatening status ***Intracavitary irradiation for recurrence 15 months after the initial treatment Table2. Serious complications and outcome Do: death from other disease, DoD: direct operative death, NED: no evidence of disease
4 津村 昌 他 284 を認 め 再 発 が 強 く疑 わ れ た(Fig.1 left)が 内 視 鏡, 生 検 で は 悪 性 所 見 は な く,経 過 観 察 と な っ た.81 か 月 後 の 透 視 で,造 影 剤 の 肺 野 へ の 大量 の 漏 出 を 認 め た(Fig.1right).食 道 切 除 と左 下肺 切 除 が 行 われ 経 過 は順 調 で あ っ た が,術 した.病 後3週 目 に突 然 死 理 組 織 学 的 に はsn1ま で の 組 織 欠 損 と, 新 鮮 な肉 芽 と古 い 肉 芽 組 織 が 認 め られ た が 腫 瘍 細 胞 は全 く認 め な か っ た.症 例6は8か 月 で 通 過 障 害 が 生 じ,24か 月で 摂 食 不 可 と な っ た ため 胃瘻 造 設 した.症 例7で は36か 月 後 よ り狭 窄 が 強 くな り60 か 月後 に 食道 抜 去,胃 管 に よ る再 建 を行 っ た.狭 窄 部 の病 理 組 織 は 粘 膜 下に 高 度 の線 維 性 肥 厚 を 呈 し,上 皮 の 異 型 性 が 高 度 に み ら れ た のみ で 腫 瘍 細 胞 は存 在 しな か っ た. 外 照 射 量 と腔 内 照 射 の線 量 に よ る障 害 の 程 度 を グラ フ に 示 した(Fig.2),症 例4は 局 所 再 発 例 の 腔 内照 射 再 施 行 例 の 為除 外 し た.症 例 数が 少 な く有 意差 は な い が 外 照 射 単独 群 に比 し,腔 内 照 射 例 で は障 害 が 強 くな る傾 向 に あ っ た.ま た腔 内 照 射 例 で は 外 照 射 量 と腔 内 照 射 線 量 の 合 計 が70Gyを 超 え る と障 害 が 強 くな る傾 向 で あ った. 考 案 Fig. I. 59-year-old female (case 5) (left) Esophagography 70months after radiotherapy: a fistula formation (arrow). (right) 食道 癌 放 射 線 治 療 後 の 合 併 症 と して の 放 射 線 脊 81months after to the lung. radiotherapy:penetration 髄 炎,心 膜 炎,放 射 線 肺 炎 な ど は,外 照 射 技 術 の 向 上,CTシ ミュ レー タ な ど の 利 用 に よ る治 療 計 画 の 精度 向 上,さ N=9 らに腔 内 照 射 の併 用 な ど に に よ り減 っ て い る1個')し か し長期 生 存 例 が 増 加 す る につ れ,治 療 後 あ る程 度 の 期 間 の後 に 生 じ る高 度 grade O-1 の狭 窄 や瘻 孔 な どの 外 科 的 処 置 が必 要 とな る 重篤 grade 2-3 な 合併 症 は 今 だ に 問題 とな る こ とが 多い5)-7). 放 射 線 治 療 にお い て照 射 線 量 が 多 くな れ ば 合併 症 の頻 度 お よ び程 度 は 高 くな る が,食 道癌 の 放 射 線 治 療 で は そ の 至適 線 量 の 幅 は非 常 に 狭 い もの と 思 わ れ る.外 照 射 単独 の 至 適 線 量に つ い て は,お お む ね7(IGy程 度 の線 量 の 報 告 が 多 い12)13.一 方, 障害 につ い て は,脊 髄 の 耐 容量 や範 囲,.回 は 照射 す る部 位 線 量 な ど に に 依 存 す る と言 わ れ る が 臨床 的 に は50Gy/25fr/5w程 度 と され,通 常 の 分 割 照 射 で50Gyで は 脊髄 炎が 生 じる 可能性 は少 ない1415). 多 分割 照 射 に よ り晩 発 障 害 と して の 脊髄 炎 の 発 症 の軽 減 が 期 待 され た が,予 測 に 反 して 耐 容 線 量は Fig.2. Corelation with exposure dose and complication grade. Patient no.4 was excluded because of reirradiation for recurrence. GradeO-1: requiring non-surgical management Grade2-3: requiring surgical management or life threatning status
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6 4) Lepke, R. A. and Libshitz, H. I.: Radiation-Induced Injury of the Esophagus. Radiology. 148: , ) Hyden, E. C., Langholz, B., Tilden, T. et al.: External beam and intraluminal radiotherapy in the treatment of carcinoma of the esophagus. J. Thorac Cardiovasc Surg. 96: , ) Hishikawa, Y., Tanaka, S. and Miura, T.: Esophageal Fistula Associated with Intracavitary Irradiation for Esophageal Carcinoma. Radiology. 159: , ) Hishikawa, Y., Kamikonya, N., Tanaka, S. et al.: Esophageal Stricture Following High-Dose-Rate Intracavitary Irradiation for Esophageal Cancer. Radiology. 159: , ) Nakajima, T., Fukuda, H., Hosono, M. et al.: Intraluminal Irradiation for T2NO Esophageal Cancer: Effect of Patient Selection on Prognosis. Radiation Medicine. 10: , ) Sun, De-Ren: Ten-Year Follow-up of Esophgeal Cancer Treated by Radical Radiation Therapy: Analysis of 869 Patients. Int. J. Radiat. Oncol. Biol. Phys. 16: , ) Sauer, R. and Keilholz, L.: The Central Nervous System: Clinical Aspects. in Radiopathology of Organs and Tissues: ed. by Scherer, E. et al. Springer- Verlag. 1991, pp ) McCunniff, A. and Liang, M. J.: Radiation Tolerance of the Cervical Spinal Cord. Int. J. Radiat. Oncol. Biol. Phys. 16: , ) Wong, C. S., Dyk, J. V., Milosevic, M. et al.: Radiation Myelopathy following Single Courses of Radiotherapy and Retreatment. Int. J. Radiat. Oncol. Biol. Phys. 30: , ) Shrieve, D. C., Wara, W. M., Edwards, M. S. B. et al.: Hyperfractionated Radiation Therapy for Gliomas of the Brainstem in Children and in Adults. Int. J. Radiat. Oncol. Biol. Phys. 24: , ) Ang, K. K., Price, R. E., Stephens, L. C. et al.: The Tolerance of Primate Spinal Cord to Re-irradiation. Int. J. Radiat. Oncol. Biol. Phys. 25: , ) Yamada, S., Kakuto, Y., Sakamoto, K. et al.: An Analysis of Autopsied Esophageal Carcinoma Treated with Irradiation. J. Jpn. Soc. Ther. Radiol. Oncol. 6: 21-27, 1994.
7 38: , ) Tsujii, H., Tsuji, H., Inada, T. et al.: Clinical Results of Fractionated Proton Therapy. Int. J. Radiat. Oncol. Biol. Phys. 25: 49-60, ) Nag, S., Abitbol, A. A., Anderson, L. L. et al.: Consensus Guideline for High Dose Rate Remote Brachytherapy in Cervical, Endometrial, and Endobronchial Tumors. Int. J. Radiat. Oncol. Biol. Phys. 27: , ) Marinello, G., Pierquin, B., Grimard, L. et al.: Dosimetry of Intraluminal Brachytherapy. Radiother. Oncol. 23: , ) Taub, S., Rodan, B. A., Bean, W. J. et al.: Balloon Dilatation of Esophageal Strictures. Am. J. Gastroenterol. 81: 14-18, ) Song, H. Y., Choi, K. C., Kwon, H. C. et al.: Esophageal Strictures: Treatment with a New Design of Modified Gianturco Stent. Radiology. 184: , ) Coia, L. R., Myerson, R. J. and Tepper, J. E.: Late Effects of Radiation Therapy on the Gastrointestinal Tract. Int. J. Radiat. Oncol. Biol. Phys. 31: , 1995.
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