External beam radiation therapy with or without high-dose-rate intraluminal brachytherapy for patients with superficial esophageal carcinoma
1999; Wiley; Volume: 86; Issue: 2 Linguagem: Inglês
10.1002/(sici)1097-0142(19990715)86
ISSN1097-0142
AutoresYasumasa Nishimura, Yoshishige Okuno, Koji Ono, Michihide Mitsumori, Yasushi Nagata, Masahiro Hiraoka,
Tópico(s)Esophageal and GI Pathology
ResumoCancerVolume 86, Issue 2 p. 220-228 Original ArticleFree Access External beam radiation therapy with or without high-dose-rate intraluminal brachytherapy for patients with superficial esophageal carcinoma Yasumasa Nishimura M.D., Ph.D., Corresponding Author Yasumasa Nishimura M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, Japan Department of Radiology, Kinki University School of Medicine, Osaka-Sayama, JapanDepartment of Radiology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan===Search for more papers by this authorYoshishige Okuno M.D., Yoshishige Okuno M.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorKoji Ono M.D., Ph.D., Koji Ono M.D., Ph.D. Research Reactor Institute, Kyoto University, Osaka, JapanSearch for more papers by this authorMichihide Mitsumori M.D., Ph.D., Michihide Mitsumori M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorYasushi Nagata M.D., Ph.D., Yasushi Nagata M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorMasahiro Hiraoka M.D., Ph.D., Masahiro Hiraoka M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this author Yasumasa Nishimura M.D., Ph.D., Corresponding Author Yasumasa Nishimura M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, Japan Department of Radiology, Kinki University School of Medicine, Osaka-Sayama, JapanDepartment of Radiology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan===Search for more papers by this authorYoshishige Okuno M.D., Yoshishige Okuno M.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorKoji Ono M.D., Ph.D., Koji Ono M.D., Ph.D. Research Reactor Institute, Kyoto University, Osaka, JapanSearch for more papers by this authorMichihide Mitsumori M.D., Ph.D., Michihide Mitsumori M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorYasushi Nagata M.D., Ph.D., Yasushi Nagata M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this authorMasahiro Hiraoka M.D., Ph.D., Masahiro Hiraoka M.D., Ph.D. Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, JapanSearch for more papers by this author First published: 20 November 2000 https://doi.org/10.1002/(SICI)1097-0142(19990715)86:2 3.0.CO;2-OCitations: 35AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract BACKGROUND Clinical results of external beam radiation therapy (RT) with or without intraluminal brachytherapy (IBT) for patients with superficial esophageal carcinoma were evaluated retrospectively. METHODS Between 1985 and 1996, 21 patients with superficial esophageal squamous cell carcinoma were treated by external beam RT, with or without high dose rate IBT, with curative intent. There were 18 males and 3 females; their median age was 67 years (range, 51–85 years). Eight patients were treated by external beam RT alone (60–69 gray [Gy]), whereas the remaining 13 patients were treated by IBT after external beam RT. Most patients in the IBT group received 2 or 3 fractions of IBT of 4 Gy after external beam RT of 50–56 Gy. RESULTS All of the 21 tumors showed complete regression at the end of RT. Local recurrence was noted in 4 patients in the group that received external beam RT alone and in 2 patients in the IBT group. Salvage therapy was successful for 4 patients. Local control probability and cause specific survival probability for the IBT group were significantly higher than those for the group that received external beam RT alone (P < 0.05 for both). The 3-year local control and cause specific survival rates for the IBT group were 85% and 100%, respectively, whereas those for the external beam RT group were 45% and 67%, respectively. Transient esophageal ulcers were noted in two patients in the IBT group. CONCLUSIONS External beam RT and IBT is a safe and effective treatment modality for patients with superficial esophageal carcinoma. Cancer 1999;86:220–8. © 1999 American Cancer Society. The rate of superficial esophageal carcinoma (T1; International Union Against Cancer, 1997) relative to the incidence of all esophageal carcinomas has increased in Japan, mainly due to the availability of Lugol dye endoscopy.1, 2 According to the Japanese Committee for Registration of Esophageal Cancer, the percentage of superficial esophageal carcinoma among all cases of resected esophageal carcinoma in Japan between 1984 and 1986 was 16.1%, whereas the value between 1978 and 1980 was 8.8%.3 In some major Japanese institutions, the percentage of superficial esophageal carcinoma among patients treated by surgery between 1985 and 1989 was 23%.2 In addition to the use of Lugol dye endoscopy, mass endoscopy screening programs are pursued to detect esophageal carcinoma among patients with head and neck carcinoma or among high risk patients, such as alcoholics.4, 5 Although surgery is currently the treatment of choice for superficial esophageal carcinoma,2, 6-11 radiation therapy (RT) has been performed on patients with morbid conditions or double carcinomas. The number of patients with superficial esophageal carcinoma treated by definitive RT has increased in Japan.12-17 Since the introduction of a high dose rate (HDR) remote afterloading brachytherapy machine at Kyoto University Hospital, HDR intracavitary brachytherapy (IBT) has been used in the treatment of superficial esophageal carcinoma. Because superficial esophageal tumors are located within the depth of the esophageal mucosa, good spatial dose distribution of IBT may improve the clinical results. The purpose of the current study was to analyze the clinical results of RT with or without IBT in the treatment of superficial esophageal carcinoma retrospectively and to discuss the optimal combination of external beam RT and HDR-IBT for the disease. MATERIALS AND METHODS Patient Population Between August 1985 and August 1996, 21 patients with superficial esophageal carcinoma were treated by definitive RT at Kyoto University Hospital and its affiliated hospitals. There were 18 men and 3 women with an average age of 68.7 years (range, 51–85 years). For 4 patients, esophageal carcinoma was detected as the second or third carcinoma when the prior carcinomas were clinically controlled. The other 4 patients had simultaneous double carcinoma. For these patients, simultaneous superficial esophageal carcinoma was detected by screening upper gastrointestinal endoscopy in 3 patients with head and neck carcinoma and in 1 patient with gastric carcinoma. For 3 patients, RT for superficial esophageal carcinoma was started after completion of the treatment of the other carcinoma. One patient with oral floor carcinoma received RT for both tumors. The indications for definitive RT were refusal of surgery for 7 patients, age >80 years for 5 patients, medically inoperable or poor general condition for 5 patients, histologically positive margin after endoscopic mucosal resection (EMR) of the tumors for 3 patients, and simultaneous double carcinoma for 1 patient. The EMR procedure for superficial esophageal carcinoma has been described elsewhere.5 All of the tumors were located in the thoracic esophagus and were squamous cell carcinoma histologically. Tumor length ranged from 0.8 cm to 7.0 cm, with an average of 2.6 cm. To assess the depth of the primary tumors, endoscopic ultrasound was performed in 7 tumors. Of the 7 tumors, maximum tumor invasion was in the mucosal layer in 3 tumors and in the submucosal layer in 4 tumors. In the remaining 14 tumors, tumor depth was estimated as superficial (mucosal or submucosal tumor invasion) by the endoscopic and radiographic appearance of the tumor.1 No patients had enlarged mediastinal lymph nodes of >5 mm on computed tomography (CT). Because our previous study revealed that the optimal size criterion in the detection of mediastinal lymph node metastasis was 5 mm,18 all of the patients were classified with T1N0M0 disease. Radiation Therapy External beam RT was given by 6 MV, 10 MV, or 15 MV X-ray. Of the 21 patients, 8 were treated by external beam RT alone, whereas 13 patients were treated by IBT after external beam RT. In 1991, we changed the treatment policy for superficial esophageal carcinoma and started a protocol of external beam RT combined with IBT. However, 2 patients treated by accelerated hyperfractionation (AHF) after 1991 were not treated by IBT. Thus, the group that received external beam RT alone consisted of all 6 patients who were treated before 1990 and the 2 patients who were treated by AHF after 1991. None of the patients were treated by chemotherapy. In the group that received external beam RT alone, 5 patients were treated by conventional fractionation (CF) and 3 were treated by AHF. In patients treated by CF, 40–46 gray (Gy)/1.8 Gy or 2.0 Gy were delivered with an anterior and posterior opposing portal. Thereafter, a 10–20 Gy/2.0 Gy boost was administered to the primary tumor by the rotation or oblique opposing parallel method to avoid excessive irradiation to the spinal cord. Total external beam RT dose ranged from 60 Gy to 69 Gy (median, 66 Gy). The initial RT field included a minimum 3-cm margin from the superior and inferior margins of the tumor and a width of 6–8 cm. To identify the tumor area at the simulation of the RT field, small radio-opaque metals were clipped at the superior and inferior margins of the tumor using endoscopy. Three patients in the group that received external beam RT alone were treated by concomitant boosts AHF. The method used to deliver AHF was described previously.19 Briefly, "large" radiation fields encompassing primary tumors with a minimum 3-cm margin received 2.0 Gy by an anterior and posterior opposing portal, and "boost" fields to the primary tumors with 1-cm margin received 1.2 Gy using an oblique opposing parallel portal at a 6-hour interval. The spinal cord was excluded from the "boost" field. The total RT dose ranged from 60 Gy to 64 Gy (median, 64 Gy). The external beam RT technique for the IBT group was the same as that for the group that received external beam RT alone. In 12 patients, external beam RT of 50–56 Gy/1.8–2.0 Gy was given by CF, and a total of 66 Gy was given by AHF in 1 patient. Within 1 week of the completion of external beam RT, IBT was started once or twice a week. All of the patients were treated with HDR-IBT using a 60Co or 192Ir source. An HDR remote afterloader with 60Co source (Ralstron; Shimadzu Co. Ltd., Kyoto, Japan) was used in 4 patients who were treated between 1991 and 1992. Starting in 1993, 9 patients were treated with an HDR brachytherapy unit containing a 370 GBq 192Ir source (micro-Selectron HDR; Nucletron Co. Ltd., Veenendaal, the Netherlands). After premedication with atropine sulfate and mild sedatives, a rubber gastric tube of 10 mm in outer diameter or a special double lumen applicator of 15 mm or 20 mm in outer diameter (MS type applicator for the esophagus; Create Medic Co., Ltd., Yokohama, Japan) was inserted into the esophageal lumen. The position of the applicator was monitored by fluoroscopy and was adjusted to cover the tumor area by the applicator. In the case of double lumen applicators, each lumen of the applicator was inflated by air until the double lumen applicator was inflated to the indicated diameter. After a dummy source was inserted into the applicator, radiographs of the applicator were taken (Fig 1a). As a centering device, a gastric tube of 10 mm was used in 2 patients, a 15-mm applicator was used in 4 patients, and a 20-mm applicator was used in 7 patients. Hishikawa et al., who are pioneers of HDR-IBT for esophageal carcinoma, used a rubber gastric tube of 10 mm in outer diameter as a centering device, because no specially designed applicator was available before 1991, and the gastric tubes were well suitable for advanced esophageal carcinomas.13, 14 The double lumen applicator of 15 mm for esophageal carcinoma became available in 1992, and a 20-mm applicator was available commercially only after 1995. In the current study, we preferred a 20-mm applicator for superficial esophageal carcinoma, which could stretch the esophageal mucosa and fit the mucosa with the surface of the applicator. Figure 1Open in figure viewerPowerPoint (a) A case of superficial esophageal carcinoma in the middle of the thoracic esophagus. After external beam radiation therapy (RT) of 56 grays (Gy), 3 fractions of intraluminal brachytherapy (IBT) of 4 Gy at the reference point were administered using a centering applicator of 20 mm in diameter. The double lumen applicator was inflated by air. The esophageal mucosa is delineated by arrowheads, and the dwell positions of the source are indicated by X. (b) Dose distribution curves for a superficial esophageal tumor. The tumor length was 3 cm, and the irradiated length was 5 cm. When 4 Gy were delivered to the reference point (indicated by "a," 5 mm from the applicator surface and 15 mm from the source), the mucosal surface (10 mm from the source) received 6.4 Gy. Figure 1 illustrates a representative patient who was treated with a centering device of 20 mm in diameter and the dose distribution around the source. The geometrically optimized dose distributions were generated using a software program (PLATO; Nucletron Co. Ltd.). The reference point of dose calculation was at a distance of 5 mm from the applicator surface.20 When an applicator of 20 mm in diameter was used, the reference isodose was located 15 mm from the source (Fig. 1b). In 12 patients, 2 or 3 fractions of 4 Gy at the reference point were given by IBT after external beam RT of 50–56 Gy/1.8–2.0 Gy. In the remaining patient in the IBT group, 2 fractions of 5 Gy of IBT were given after AHF of 66 Gy. The overall treatment time (OTT), including external beam RT and brachytherapy, ranged from 46 days to 77 days (mean, 55 days). Evaluation of Tumor Response Response of the primary tumor was assessed by serial esophagography, endoscopy, and biopsies. Esophagography and/or endoscopy were performed every 3–4 months for asymptotic patients, and any clinically suspected tumor recurrence required biopsy and histopathologic proof. CT scans were obtained at 6-month intervals for most patients and were used for evaluation of primary tumor recurrence and regional lymph node recurrence. Local control was defined as a lack of either clinical or pathological evidence of tumor recurrence in the esophagus. Smooth narrowing of esophageal lumen on esophagograms was regarded as local control unless biopsy revealed malignant cells. Statistical Methods Overall survival, cause specific survival, and local control rates were calculated from the first date of external beam RT. Overall survival included deaths due to any cause. Cause specific survival included deaths due to esophageal carcinoma, whereas patients who died of intercurrent disease were counted as withdrawn alive. Local control and survival rates were plotted using the Kaplan–Meier method. The difference in local control or survival curves during the entire follow-up period was assessed by the log-rank test, and a P value of <0.05 was regarded as significant. RESULTS Follow-Up Period As of February 1999, 6 patients had died within 13–25 months of the treatment. Among them, only 1 patient in the group that received external beam RT died of recurrent esophageal carcinoma, whereas the remaining 5 patients (3 in the group that received external beam RT and 2 in the IBT group) died of intercurrent diseases, including brain infarct, pulmonary failure, and renal failure, without evidence of recurrence of esophageal carcinoma. Median follow-up for the other 15 patients was 60 months after the treatment, with a minimum follow-up of 29 months. Eight patients were followed for more than 60 months. Local Control and Survival Rates Figure 2 shows local control probabilities of esophageal carcinoma for the group that received external beam RT alone and the IBT group. Local control probability for the IBT group was significantly higher than that for the group that received external beam RT alone (P < 0.05), and the local control rates at 3 years for the groups were 85% and 45%, respectively. All of the 21 tumors showed complete regression at the end of RT. Four of the 8 tumors in the group that received external beam RT alone and 2 of the 13 tumors in the IBT group showed local recurrence. No regional lymph node recurrence was noted in the 21 patients. One local recurrence in the group that received external beam RT alone was noted out of the RT field in the cervical esophagus, and another recurrence in the group that received external beam RT alone was noted within the RT field that had received 48 Gy in total. The remaining 4 local recurrences were noted in the definitive RT field that had received >60 Gy. In both groups, all local recurrences were detected within 2 years of the treatment (Fig. 2). Figure 2Open in figure viewerPowerPoint Local control curves for superficial esophageal carcinoma according to treatment methods. Local control probability of the intraluminal brachytherapy (IBT) group was significantly higher than that of the group that received external beam radiotherapy (ext RT) alone (P < 0.05). Subtotal esophagectomy was performed in 3 patients who had a local recurrence, and all of them were salvaged successfully. One tumor in the group that received external beam RT alone showed local recurrence 4 months after RT. Because the general condition of the patient was not good enough for salvage operation, three cycles of chemotherapy (150 mg of cisplatin and 110 mg of pepleomycin in total) were administered. The recurrent tumor regressed completely by chemotherapy, and local control was continued until the patient died of cerebral infarction 12 months after chemotherapy. Cause specific survival rates and overall survival rates at 3 years were 67% and 50%, respectively, for the group that received external beam RT alone and 100% and 85%, respectively, for the IBT group (Figs. 3, 4). The cause specific rate for the IBT group was significantly higher than that for the group that received external beam RT alone (P < 0.05; Fig. 3). The difference in the overall survival rate was marginally significant (P < 0.10; Fig. 4). This difference in overall survival rate may be due in part to the deaths from intercurrent diseases. Three of 8 patients in the group that received external beam RT died of intercurrent diseases, whereas 2 of 13 patients in the IBT group died of an intercurrent disease. Figure 3Open in figure viewerPowerPoint Cause specific survival curves for superficial esophageal carcinoma according to treatment method. The cause specific survival probability for the intraluminal brachytherapy (IBT) group was higher than for the group that received external beam radiation therapy (ext RT) alone (P < 0.05). Figure 4Open in figure viewerPowerPoint Overall survival curves for superficial esophageal carcinoma according to treatment method. The difference between the survival curves was marginally significant (P < 0.10). IBT: intraluminal brachytherapy; ext RT: external beam radiation therapy. Local Control and Overall Treatment Time The correlation between local control and OTT was analyzed, because the importance of OTT has been demonstrated for esophageal squamous cell carcinomas.19, 21, 22 Overall treatment time ranged from 27 days to 54 days, with a median of 49 days in the group that received RT alone, whereas it ranged from 46 days to 77 days, with a median of 52 days, in the IBT group. In this analysis, two local recurrences that were noted out of the RT field or within the RT field that had received 48 Gy were excluded, and only recurrences in the definitive RT dose region were considered. In the group that received external beam RT alone, no local recurrence in the full dose region was observed for patients with OTT ≤ 7, whereas 2 of the 3 patients with OTT > 7 weeks showed local recurrence in the full dose region. In the IBT group, 2 of the 4 patients with OTT > 8 weeks showed recurrence in the full dose region, whereas none of the 9 patients with OTT ≤ 8 weeks showed local recurrence. Because the number of patients was small, no significant difference in local control rates according to OTT was observed. Acute and Late Toxicities IBT after external beam RT was well tolerated by all patients. Acute esophagitis and swallowing pain were the only acute toxicities associated with IBT. For these patients, sodium alginate solution (Alloid G; Kaigen Co., Ltd., Osaka, Japan) was administered at a dose of 20 mL three or four times daily, and these symptoms healed within 2–3 weeks. With regard to late complications of RT, 2 esophageal ulcers and 1 esophageal stenosis were noted in the IBT group. Asymptomatic esophageal stenosis was noted in 1 patient 18 months after AHF combined with IBT. Esophageal ulcer was observed only in patients who were treated by centering applicators of 10–15 mm in diameter (4 Gy × 3 fractions) after conventional RT of 50 Gy or 56 Gy, whereas none of the 7 patients treated with applicators of 20 mm in diameter showed esophageal ulcer or stenosis. Esophageal ulcers were noted 1 year and 3 years after treatment, and both patients healed within several months of conservative treatment. Figure 5 shows the changes in dose distribution according to the diameter of the centering applicators. When 4 Gy were delivered to the reference point by a 10-mm applicator, the dose to the mucosal surface was 8.6 Gy (2.15 times the prescribed dose). Conversely, when 4 Gy were delivered to the reference point by a 20-mm applicator, the dose to the mucosal surface was 6.5 Gy (1.62 times the prescribed dose). Thus, the diameter of the centering applicator is important for the dose to the esophageal mucosa. Figure 5Open in figure viewerPowerPoint Changes in dose distributions according to the diameter of the centering applicators. The reference dose point is at a distance of 5 mm from the applicator surface. For a 10-mm applicator, the reference point is 10 mm from the source, and it is 15 mm from the source for a 20-mm applicator. When 400 centigray (cGy) were delivered to the reference point by a 10-mm applicator, the dose to the mucosal surface (5 mm from the source) was 860 cGy (2.15 times the prescribed dose). Conversely, when 400 cGy were delivered to the reference point by a 20-mm applicator, the dose to the mucosal surface (10 mm from the source) was 650 cGy (1.62 times the prescribed dose). DISCUSSION In the current study, external beam RT with or without IBT showed excellent local control and survival rates for superficial esophageal carcinoma. The 5-year local control rate, cause specific survival rate, and overall survival rate for the 21 patients were 71%, 89%, and 71%, respectively. Table 1 shows a summary of the literature on RT for superficial esophageal carcinoma.12-17 Okawa et al.17 reported the clinical results of 105 patients with superficial esophageal carcinoma who were treated with definitive RT at 15 Japanese institutions between 1981 and 1990. In the multiinstitutional analysis, the 2-year local control rate was 83%, and the 5-year cause specific survival and overall survival rates were 71% and 39%, respectively. The 5-year cause specific survival rates by definitive RT for patients with superficial esophageal carcinoma reported so far range from 62% to 80% (Table 1). These cause specific survival rates were quite comparable to those from surgical series, although the overall survival rates were lower compared with the high cause specific survival rates due to intercurrent deaths. Table 1. Clinical Results of Radiation Therapy for Patients with Superficial Esophageal Carcinoma Study No. of patients Ext RT (Gy; range) IBT dose rate (Gy; fraction) Fr size (Gy) Distance (mm)a OTT Five-yr survival rate (%) Cause specific Overall Hishikawa et al., 198513 5 50–60 6–12 (1–2 fr HDR) 6 10 6–7 weeks 80 (4 of 5 at 1 yr) — Hishikawa et al., 198914 6 — 18–24 (3–4 fr HDR) 6 10 2 weeks All patients survived for 6–16 mos — Okawa et al., 199416 18 Median, 70 (50–76) — — — NM — — 3 60 6–12 (1–2 fr MDR) 6 9 NM — — 21 (total) — — — — — 62 41 Okawa et al., 199517 58 Mean, 66 (40–84) — — — NM 72 — 47 Mean, 53 (30–70) Mean, 11.7 (2–3 fr HDR, MDR, LDR) — NM NM 70 — 105 (total) — — — — — 71 39 Itoh et al., 199615 15 Median, 64 (63–71) — — — NM — — 9 Median, 56 (30–60) 6–20 (2–4 fr HDR, LDR) 4b 10.0–12.5 NM — — 24 (total) — — — — — 80 37 Akagi et al., 199712 26 Median, 60 (50–61.2) 10 (2–5 fr) 2–5 12.5 Median, 64 d (48–79 d) 76 (at 3 yrs) — Current series 8 Median, 64 (60–69) — — — Median, 49 d (27–54 d) 67 50 13 Median, 50 (50–66) 8–12 (2–3 fr HDR) 4 10–15 Median, 52 d (46–77 d) 100 92 21 (total) — — — — — 89 76 Ext RT: external beam radiotherapy; IBT: intraluminal brachytherapy; OTT: overall treatment time; Gy: gray; Fr: fraction; HDR: high dose rate; MDR; middle dose rate; LDR: low dose rate; NM: not mentioned; d: days. a Distance of reference point of dose calculation from the source. For all series, the reference point of dose calculation was 5 mm from the applicator surface. b Fraction size for HDR IBT. The survival probability for patients with resected superficial esophageal carcinoma is related strongly to the depth of tumor invasion.6-11 For mucosal tumors, the 5-year survival rates for most Japanese institutions are approximately 90%, ranging from 64% to 100 %. For submucosal tumors, the 5-year survival rates are approximately 50%, ranging from 48% to 60%. This difference in prognosis is attributable to the presence of lymph node metastases in submucosal tumors. The percentages of lymph node metastases for patients with resected submucosal esophageal tumors are 36–50%, whereas those for patients with mucosal tumors are 0–10%.2, 6, 9, 10 Therefore, external beam RT to the regional lymph nodes is necessary in the treatment of patients with superficial esophageal carcinoma that invades the submucosal layer. Because no recurrence of regional lymph nodes was noted in the current series, external beam RT of 50–56 Gy may be enough to control CT negative metastatic lymph nodes. Of the 6 patients with local recurrences in the current study, 4 were salvaged by surgery or chemotherapy. Because most of the local recurrences of superficial esophageal carcinoma were still located within the submucosal layer, and salvage treatments were performed successfully in the patients with early local recurrences. The high cause specific survival rate is attributable to the success of salvage treatments. Thus, RT with IBT is a good alternative to subtotal esophagectomy for patients with superficial esophageal carcinoma considering the excellent results of salvage surgery. The effects of OTT in the treatment of patients with head and neck carcinoma, uterine cervical carcinoma, and esophageal carcinoma have been investigated intensively.19, 21-24 These tumors are predominantly squamous cell carcinoma and grow rapidly.22, 24 Kajanti et al.21 analyzed the effects of OTT on local control rates in 353 patients with esophageal carcinoma treated with RT. They calculated RT doses for 10% probability of tumor control at 1 year (TCD10) and demonstrated that the TCD10 did not change significantly from 6 weeks to 7 weeks, but it increased at 8 weeks and 9 weeks. In the current analysis, a higher local failure rate was noted in patients with OTT > 8 weeks in the IBT group, although no significant difference in local control rate according to OTT was demonstrated. The lack of statistical significance may be attributable to the small numbers of tumors in the current analysis. Although no hard data exist for T1 tumors, it is better to keep OTT as short as possible, even for patients with superficial esophageal carcinoma. A recent advance in the treatment of esophageal carcinoma is chemoradiation therapy.25-28 The superiority of chemoradiation therapy to RT alone has been demonstrated by several randomized clinical trials.25, 27 In the current analysis, no patients were treated with any kind of chemotherapy. However, high local control and overall survival rates were obtained by external beam RT combined with IBT. The tumor volume of superficial esophageal carcinoma can be covered easily within the isodose curve of the reference dose. Improvement of the spatial dose distribution by IBT may have improved the clinical results. Thus, chemoradiation therapy may not be necessary for superficial esophageal carcinoma when appropriate IBT is combined with external beam RT. Esophageal ulcer is a common late toxicity in IBT for esophageal carcinoma.13, 14, 17, 20, 29 Hishikawa et al.13, 14 reported that 6 of 11 patients with superficial esophageal carcinoma treated by IBT alone or IBT with external beam RT developed esophageal ulcer. In the Japanese multiinstitutional analysis for superficial esophageal carcinoma, late complications, including esophageal ulcer and fistula, were significantly higher in the group that received external beam RT with IBT than in the group that received external beam RT alone.17 In addition, 3 patients in the group that received external beam RT plus IBT died of late complications, including esophageal fistula and bleeding. This high complication rate apparently is related to the high fraction size of HDR-IBT. In fact, Hishikawa et al.13, 14 used a fraction size of 6 Gy at 5 mm from the surface of a 10-mm applicator. Although we reduced the fraction size to 4 Gy in the current study, there were still two esophageal ulcers. However, there were few late complications in patients treated with 20-mm applicators. Because the dose to the esophageal mucosa can be reduced by increased applicator diameter (Fig. 5), we recommend using 20-mm applicators for patients with superficial esophageal carcinoma. The place of IBT in the treatment of patients with superficial esophageal carcinoma is still a question to be answered. In the multiinstitutional analysis by Okawa et al.,17 a slightly higher 2-year local control rate was obtained in the group that received external beam RT with IBT (90%) than in the group that received external beam RT alone (77%). However, the cause specific 5-year survival rates were approximately 70% for both groups (Table 1). In the current study, the local control probability for the IBT group was significantly higher than that for the historic control of the group that received external beam RT alone (Fig. 2), which resulted in an improved cause specific survival rate for the IBT group compared with the group that received external beam RT alone (Fig. 3). The 5-year local control and cause specific survival rates for the group that received external beam RT with IBT were 85% and 100%, respectively. Thus, the local control and cause specific survival rates in patients treated with IBT combined with external beam RT were excellent. Recently, the results of a Japanese multiinstitutional, prospective, randomized trial comparing external beam RT alone versus external beam RT with IBT for patients with esophageal carcinoma were presented at the 1998 Annual Meeting of American Society for Therapeutic Radiology and Oncology.23 After patients received 60 Gy of external beam RT, a total of 103 patients were randomized to either 10 Gy/5 fractions boost of external beam RT alone or 10Gy/2 fractions of IBT. Compared with external beam RT alone, the survival benefit of RT with IBT for patients with esophageal carcinoma was observed only for the patients with relatively early esophageal carcinoma with tumors <5 cm in length or T1,T2 stages. Because the study included patients with both superficial and locally advanced esophageal carcinoma, the contribution of IBT to the treatment of patients with superficial esophageal carcinoma should be evaluated in a future randomized trial. 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Int J Radiat Oncol Biol Phys 1998; 42(Suppl 1): 199. Citing Literature Volume86, Issue215 July 1999Pages 220-228 FiguresReferencesRelatedInformation
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